Biomarker

Biomarkers 101  

If you’ve recently been diagnosed with cancer or begun cancer therapy, you’ve probably had to learn a lot of new terms related to your cancer type, treatment, and the challenges of living with cancer. “Biomarker” is a term you may not be familiar with. Researchers are paying more attention to the role biomarkers play in cancer cell development, growth, and spread as they understand more about how cancer cells form, grow and spread. Understanding cancer biomarkers is critical to designing a treatment strategy that is suited for you, even if it doesn’t seem clear at first. 

A cancer biomarker is a substance or activity that can be used to detect the presence of cancer in the body. A biomarker (short for biological marker) may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer. 

Patients with the same cancer type used to receive the same treatment, but research has revealed that tumors, even within the same cancer type, have distinct characteristics. Physicians are increasingly relying on cancer biomarkers to learn more about a patient’s tumor and forecast which treatment will be most effective against their specific cancer. 

 

What Is a Biomarker? 

Cancer biomarkers are biological substances produced by a cancer patient’s body or tumor. Biomarker testing aids in the identification of tumor changes. Biomarkers are particular to the tumor DNA, RNA, protein, or metabolomic profiles. Genomic testing, which examines the DNA sequence, DNA or RNA tests to look for gene fusions, and tests to assess RNA or protein levels are all examples of testing. 

Biomarkers can be used for several purposes: 

• Assess an individual’s risk of developing cancer 
• Determine an individual’s risk of cancer recurrence 
• Predict the likelihood that a given therapy will work for a specific patient 
• Monitor a disease’s progression to determine if a therapy is working 

After biomarkers have been identified, the next step is to see if any of the changes are actionable, or if there is a genetic change driving tumor growth that can be addressed with an existing medicine. 

Although there is a lot of effort on developing novel targeted therapy medications that disrupt key drivers of cancer growth, not all cancer types have biomarkers that can be identified right now. Biomarker-guided treatment has been demonstrated to extend patients’ lifespan in studies. Researchers study new ways to identify and treat cancer with biomarkers in clinical trials. 

 

What Are Examples of Biomarkers? 

Notable examples of potentially predictive cancer biomarkers include: 

• mutations on genes KRAS, p53, EGFR, erbB2 for colorectal, esophageal, liver, and pancreatic cancer. 
• mutations of genes BRCA1 and BRCA2 for breast and ovarian cancer. 
• abnormal methylation of tumor suppressor genes p16, CDKN2B, and p14ARF for brain cancer. 
• hypermethylation of MYOD1, CDH1, and CDH13 for cervical cancer  and hypermethylation of p16, p14, and RB1, for oral cancer. 

 

Types of Biomarkers 

There are two main types of tumor markers: circulating tumor markers and tumor tissue markers.  

Circulating tumor markers can be found in the blood, urine, stool, or other bodily fluids of some patients with cancer. Circulating tumor markers are used to: 

• estimate prognosis 
• determine the stage of cancer 
• detect cancer that remains after treatment (residual disease) or that has returned after treatment 
• assess how well a treatment is working 
• monitor whether the treatment has stopped working 

Although an elevated level of a circulating tumor marker may suggest the presence of cancer and can sometimes help to diagnose cancer, this alone is not enough to diagnose cancer. For example, noncancerous conditions can sometimes cause the levels of certain tumor markers to increase. In addition, not everyone with a particular type of cancer will have a higher level of a tumor marker associated with that cancer. Therefore, measurements of circulating tumor markers are usually combined with the results of other tests, such as biopsies or imaging, to diagnose cancer. 

Tumor tissue (or cell) markers are found in the actual tumors themselves, typically in a sample of the tumor that is removed during a biopsy. Tumor tissue markers are used to: 

• diagnose, stage, and/or classify cancer 
• estimate prognosis 
• select an appropriate treatment (e.g., treatment with a targeted therapy) 

Tumor tissue markers that indicate whether someone is a candidate for a particular targeted therapy are sometimes referred to as biomarkers for cancer treatment. Tests for these biomarkers are usually genetic tests that look for changes in genes that affect cancer growth. 

 

Do All Cancers Have Biomarkers? 

Some people’s DNA contains genes that can suggest an elevated risk of acquiring certain cancers. A person with particular mutations in BRCA1 and BRCA2, the so-called “breast cancer genes,” for example, has an increased risk of developing breast, ovarian, prostate, and other cancers. 

Most tumors, however, are not hereditary, and the vast majority of people diagnosed with cancer lack any of the “cancer genes” – at least none that we can currently discover. However, biomarkers exist for all cancers. 

Your cancer has a unique version of your DNA that is different from the DNA in your healthy cells. Most of the cancer biomarkers that have been associated with treatments have to do with your tumor’s unique genes and molecular structure, rather than your own genes. 

 

What Is Biomarker Testing? 

Your doctor will need to obtain a sample of tumor tissue or bodily fluid and submit it to a laboratory for a series of advanced pathology and molecular profiling tests in order to identify if, and at what amounts, specific biomarkers are present in your cancer. 

These tests will discover and analyze the amounts of biomarkers that are specific to your cancer. The data will then be compared to published research by the world’s top cancer researchers to determine which treatments are likely to work and which are not.  

Your doctor will then receive a report detailing all the biomarkers found in the sample, as well as the treatments found to be positively and negatively related to those biomarkers. This process allows your doctor to personalize your anticancer treatment plan based on your cancer’s unique biomarker profile. 

Sources:  

https://www.mdanderson.org 

https://www.mycancer.com. 

Biomarker Testing 

Biomarker testing is the analysis of a patient’s tissue and blood for specific driver mutations, multiple gene alterations, and non-genomic biomarkers (such as protein expression), with no relation to anything inherited within a family. All patients have their own individual pattern of biomarkers and DNA in cancer cells, and biomarker testing can give insight about a patient’s cancer and what treatments may be best for them. 

Biomarkers are named using 3 or 4 letter abbreviations, and some of these can influence how well treatment of cancer goes. Some drugs used to treat cancer are only effective in those with certain subtypes of cancer. Biomarker testing is only performed in those who have already been diagnosed with cancer and can be used for doctors to plan treatment. Other names for biomarker testing include tumor testing, somatic testing, genomic profiling, molecular testing, or tumor subtyping. 

How Is Biomarker Testing Performed? 

To perform biomarker testing, a sample of the tumor tissue, bodily fluid, or blood if you have a blood cancer. If surgery or a biopsy is already planned, a sample of that tissue will be taken. Then, it will be analyzed in a laboratory.  

Why Is Biomarker Testing Critical for Patients with Cancer? 

In some cancer types, biomarker testing a standard of care, meaning your doctor may test for biomarkers without having to mention or ask for it. For others, this testing is only done at major cancer centers, university hospitals, or if requested. Testing at these sites can help determine If you are eligible for clinical trials. 

To ensure the cancer is treated with the most appropriate option, it is important to perform biomarker testing prior to the first-line therapy. Biomarker testing results and benefits do not depend on any risk factors, so all patients should be encouraged to have this testing. For example, it does not matter whether lung cancer patients smoked or did not smoke. 

If chemotherapy or radiation therapy are used instead of an immunotherapy or targeted therapy because biomarker testing wasn’t performed, it could result in more healthy cells being killed and more side effects from treatment. Therefore, patients should ask about biomarker testing before treatment is planned. 

How Long Does Biomarker Testing Take? 

After the sample is collected from the patient and sent to a laboratory for analysis, results from biomarker testing can take several weeks. Once finished, a report will be returned with a list of biomarkers present in the cancer cells. It will also include which drugs or treatments that may work for you. 

Even if the results find a biomarker that matches an available treatment, the therapy is not guaranteed to work for you depending on other features of your cancer or your cells, such as how the medicine is broken down in your body. In some cases, not all cancer cells have the same biomarkers. That means that a biomarker test may find a treatment that will kill some, but not all, present cancer cells. Cancer cells that are not killed by the treatment could keep growing, preventing the treatment from working or causing the cancer to relapse shortly after completing treatment. Also, biomarkers in your cancer may change over time, so a test only captures a snapshot of the changes when the test is performed. In some patients, testing may be performed multiple times. 

Biomarker Testing Types 

There are many different types of biomarker testing depending on the biomarkers that are tested for. Some tests only check for one biomarker, while others check for many at once. These tests are known as multigene tests or panel tests. Certain cancers may require a specific type of test like melanoma, other biomarkers are seen in many cancer types. Next Generation Sequencing (NGS) looks at all the genes in your cancer. This can be most beneficial for those with a rare type of cancer. 

One type of biomarker test can be performed to look at the total number of genetic changes in the cancer and which biomarkers are present, this is known as the tumor mutational burden (TMB). The more mutations present, the higher the patient’s TMB. Cancers with a high TMB are more likely to respond to immunotherapies and targeted therapies compared to those with a low TMB. 

Benefits of Biomarker Testing 

Not all patients who get biomarker testing will receive results that show biomarkers that can be treated, however without receiving testing, patients may be unaware of all their treatment options. 

Benefits of biomarker testing include: 

• Diagnose the subtype of disease. 
• Determine eligibility for clinical trials. 
• Match patients with a targeted therapy or immunotherapy based on what biomarkers are present. 
• If treatment has already started, testing will confirm whether the correct treatment is being used. 

Biomarker tests may not help patients if: 

• Doctors are unable to safely get a biopsy. 
• Not enough tumor tissue is present in the biopsy sample to have biomarker testing done. 
• No biomarkers are found in your cancer that match with available therapies. 
• A matching therapy is found that would be used off label, but your insurance doesn’t cover the cost. 
• A matching therapy that is being tested in a clinical trial, and you are not eligible to participate in the trial due to the inclusion or exclusion criteria. 

Sources: 

https://www.cancersupportcommunity.org 

https://conquer-magazine.com 

https://www.cancer.gov 

Biomarker Testing for Cancer Treatment 

Like any organic being, our bodies go through changes. And when those normal or abnormal biological changes happen, they leave traces behind in our blood, bodily fluids, or tissues. Biomarkers are measurable medical indicators of those changes at a molecular level. They help doctors identify the presence or progress of a disease or how the body reacts to a prior or possible treatment. Any testable biological indicator can be used as a biomarker. In terms of cancer, biomarkers (or tumor marker) may be molecules created by a tumor or in response to cancer. Thus, they help characterize the changes in the tumor. 

The purposes of biomarkers are as follows: 

• Evaluate the person’s risk of developing cancer  
• Evaluate the patient’s risk of recurrence  
• Estimate how successful a treatment/therapy would be for a specific patient  
• Evaluate the success of a current treatment and the progress of the disease 

Biomarker testing is a method to search for genes, proteins, and other substances that are expected to give information about cancer. Based on the aim of the search, the testing can investigate the DNA sequence with genomic testing, gene fusions with DNA or RNA tests, or tests to assess RNA and protein levels. Sometimes, when other substances cause the body to produce the materials aimed to be identified with biomarker testing, or the levels might be affected by different body functions, additional methods, such as biopsy, can be performed. 

Biomarker testing for cancer treatment can also be named the following: 

• Tumor testing 
• Tumor genetic testing 
• Genomic testing/genomic profiling (This shouldn’t be confused with genetic testing, which aims to find out if the tested person has any inherited mutations that increase their risk of cancer. Biomarker testing does not investigate inherited mutations in general.) 
• Molecular testing/molecular profiling 
• Somatic testing 
• Tumor subtyping 

Sometimes, patients are tested to see if they are eligible for a specific drug or therapy. In this case, this test can be combined with a biomarker test to investigate if the patient’s tumor gene has a particular biomarker or gene mutation to be targeted by the intended drug. This simultaneous testing is called a companion diagnostic test. Another purpose of the companion diagnostic test is to evaluate the success of the treatment and identify any possible side effects. 

How is the Biomarker Testing Performed? 

There are two ways to collect samples for biomarker testing: biopsy and blood draw. A biopsy (also called a tissue biopsy) is preferred when the cancer patient has a solid tumor. The biopsy can be performed during a tumor removal surgery or separately. Blood drawing is the method preferred when the patient has a circulating tumor, such as blood cancer. The procedure of examining the blood for traces of cancer (such as cancer cells or DNA from the cancer cells running through the veins) is called a liquid biopsy. The blood drawing method can also be used when the solid tumor is hard to collect with a biopsy. 

Usually, the sample is collected through one of the two methods explained above and is enough to start the test in the laboratory. However, when a gene analysis is involved, healthy cell samples are also required to compare cancerous and healthy tissue and identify any genetic changes. These changes are called somatic mutations, which are not inherited and usually cause cancer or other diseases. The healthy cell sample can be collected from blood, a small piece of skin, or saliva. 

The laboratory makes the necessary pathological analysis and prepares a report showing the biomarkers in the cancer cells and lists the treatments suitable for the patient. When the medical team receives this report, they make suggestions accordingly. 

What are the Types of Biomarker Tests? 

There are different elements to categorize the biomarker tests. Some tests focus on biomarkers that indicate a particular type of cancer, and others search for biomarkers that are found in more than one type of cancer. Some biomarker tests investigate the existence of genetic markers, while others the proteins or conditions. 

Liquid biopsies are also considered a type of biomarker test, where the blood or other bodily fluids such as urine or saliva are examined for the molecules or particles coming from the cancer cells. 

Another kind of biomarker test aims to find out how many genetic mutations the patient’s tumor has gone through. These genetic changes in tumors are called the tumor mutational burden (TMB). The more genetic mutations present, the greater the TMB. 

Sometimes, the tests explore only one biomarker, and sometimes for more than one. The tests that look at multiple biomarkers are called multigene tests or panel tests. Another kind of biomarker test that explores all the genes in the cancer patient’s tumor is called whole-exome sequencing. Similar to whole-exome sequencing, whole-genome sequencing explores all the DNA of the patient’s cancer. 

How is Biomarker Used for Disease Diagnosis? 

Usually, the reason for a patient to go through biomarker testing is generally the doctor’s reading of the symptoms and signs the patient experiences. Based on the symptoms and signs and the risk factors, if there are any, the doctor shapes a medical opinion before diagnosis of the patient’s case. According to the definition given on the National Center for Biotechnology Information, “a diagnostic biomarker is a biomarker used to detect or confirm presence of a disease or condition of interest or to identify individuals with a subtype of the disease.” The biomarker testing functions as pathological evidence of the doctor’s deduction for diagnosis. 

How are Biomarkers Used in Cancer Treatment? 

The relationship between the biomarker and cancer starts with identifying any biomarkers indicating the presence of cancer. The laboratory performs pathological testing and molecular profiling to identify if the specific biomarkers are present (including its levels) in the patient’s tumor. The test results may also indicate the patient’s unavailability for specific treatment options. Or some results may not be helpful in terms of treatment option decisions. However, when biomarker testing provides useful information, then it is used to select cancer treatment options. According to the detailed report delivered by the laboratory, the medical team decides what kind of treatment or therapy, such as immunotherapy or targeted therapy, would work best on the patient and maybe develop a customized treatment. Some immunotherapy and targeted therapy options are valid for cancer patients only with specific biomarkers. This means that specific gene mutations can only be treated with the specific inhibitors that target those mutations. 

Apart from targeted therapy and immunotherapy, the biomarker identified through a test can also indicate the patient’s eligibility for advanced treatment or drug option that is being tested just before becoming widely available, focusing on their type of cancer. These drugs or therapies must go through clinical trial to be approved by the US Food and Drug Administration before it is accepted and available. Only through these trials do we know how to react against and treat specific kinds of tumors, and only through clinical trials can we explore more. Note that eligibility for a clinical trial in terms of biomarkers does not guarantee a patient’s enrollment since there are many other eligibility criteria, such as age, the existence or nonexistence of specific drug use/treatments, cancer stage, etc. 

What is the Clinical Importance of Testing the Biomarker? 

The biomarker testing helps the medical team identify the changes in patients’ genes, proteins, tissues, cells, and their bodies’ reactions to specific therapies/conditions. And based on the test results, the medical team can guide the patient to available standard treatment or encourage them to choose an innovative treatment, called the clinical trial phase. 

Each patient’s body and how it manifests, or experiences cancer is unique to their biology. Although people may have the same type of cancer or the same stage, how they respond to treatment is unique to them. That is why biomarker testing is also important in designing precision medicine (also called personalized medicine). What is precision medicine? It is an approach that includes disease prevention, diagnosis, and treatment customized to the patient’s genes, proteins, and other substances in the patient’s body. The medicine designed for the patient’s specific conditions proves better results than standards. In cancer treatment, precision medicine is designed based on the results of biomarker testing. Additional medical tests help the medical teams and patients make informed decisions about the treatments and save time from available but unhelpful treatment options. 

According to the article by Battula Srinitha published on the International Online Medical Council’s website, “Molecular biology using genomic, transcriptomic, proteomic, or metabolomic biomarkers aids in the development of precise diagnostics, especially in precision medicine. To predict disease course, track disease evolution, identify different sub-populations of patients, and predict and monitor patient response to most therapies, this precision medicine domain necessitates the identification and clinical confirmation of a large number of biomarkers.” 

Although biomarker testing is not yet very common, it is becoming conventional for some types of cancer, such as breast, colorectal, or non-small cell lung cancer, to see which treatment option works best for the patient. 

How Much Does Biomarker Testing for Cancer Treatment Cost?

This question does not have one answer. The cost depends on the patient’s type of cancer and biomarker tests they need, along with their insurance plan. The general approach of the insurance companies is to cover the biomarker tests if they do not present an experimental case, but still, what is important is the patient’s plan. State-backed insurance programs such as Medicare and Medicaid usually support biomarker testing for some types of cancer in the advanced stages. And most of the clinical trials that involve biomarker testing usually do not charge patients for the tests. If you’d like to find out if you are eligible for a clinical trial, contact us to explore your options. 

 

Sources: 

cancer.gov 

mdanderson.org 

nursingcenter.com 

iomcworld.org 

ncbi.nlm.nih.gov 

ALK and Cancer 

ALK is a genetic change in the DNA of lung cells that causes the cells to grow abnormally and eventually become cancerous. Once cancer cells begin to grow in the lungs, they can potentially spread to other parts of the body and impair its function. In this article, you can find the connection between ALK and cancer. 

  

What Is Anaplastic Lymphoma Kinase (ALK) Gene? 

Some cancers including lung involve gene mutations that affect how fast the tumor grows. The ALK mutation is one of these gene changes and stands for anaplastic lymphoma kinase. AKL makes the protein that plays a role in cell growth. It is present in the body when it is still an embryo and helps develop the intestinal and nervous systems. Mutated (altered) forms of the ALK gene and protein have been found in certain types of cancer, including neuroblastoma, non-small cell lung cancer, and anaplastic large cell lymphoma. These changes can increase the growth of cancer cells. ALK can be fused with different genes. The most common is the EML4 gene, which promotes cell migration and invasion in lung cancer cells. 

  

What is ALK-positive cancer? 

When ALK combines with another gene to cause lung cancer, this condition is called ALK-positive. 

  

Is ALK lung cancer or lymphoma cancer? 

A patient diagnosed with ALK-positive may hear the definitions of ALK-positive lung cancer or ALK-positive lymphoma cancer related to AKL. Therefore, the first questions that come to mind may be:  

• What is ALK-positive lung cancer? 
• What is an ALK-positive lymphoma cancer? 

  

ALK was first described in lymphoma, but most ALK-positive cancers are non-small cell lung cancer. When the ALK gene is changed or fused with another gene, it is called ALK fusion or ALK rearrangement.  

ALK-positive lung cancer represents about 4 percent of lung cancer. Usually, adenocarcinoma occurs in non-small cell lung cancer. Patients who are positive for ALK tend to be younger than the average lung cancer patients. It occurs in approximately 30 percent of lung cancer patients diagnosed under 40. About half of ALK-positive lung cancer patients are diagnosed before age 50. 

  

How is ALK-Positive Lung Cancer Diagnosed? 

Whether the lung cancer is ALK-positive is determined by tumor tissue or blood tests. FISH analysis (looking for changes in chromosomes through tissue under the microscope), immunohistochemistry (examination of proteins in the cell under a microscope), biomarker, and liquid biopsy (searching for tumor DNA in the blood) are the tests used for the diagnosis of ALK. 

  

What Are The ALK-Positive Lung Cancer Symptoms? 

The symptoms of ALK-positive lung cancer are no different from other types of lung cancer and include: 

• Persistent cough 
• Chest pain that worsens when coughing or laughing 
• Shortness of breath 
• Muffled sound 
• Grunt 
• Losing weight for no reason 
• Feeling weak or tired 

  

Is ALK Mutation Inherited? 

Although the ALK gene is inherited from both parents in one copy, there is no study on the familial transmission of the ALK-positive mutation. 

  

How to Treat ALK-Positive Lung Cancer? 

Knowing if your cancer is ALK-positive can help your doctor understand which treatments will work best against it and what outlook you can expect. ALK-positive lung cancer responds very well to a group of targeted drugs called ALK inhibitors. Chemotherapy, radiation therapy, immunotherapy, and other drugs also work against this cancer. 

  

What Are ALK-Inhibitors In The Treatment Of Cancer? 

Inhibitors used in the treatment of ALK-positive cancer are:  

• Crizotinib (Xalkori) 
• Ceritinib (Zykadia) 
• Alektinib (Alecensa) 
• Brigatinib (Alunbrig) 
• Lorlatinib (Lorbrena) 

When ALK is positive, cancer is likely to develop within 1-2 years, and the ALK inhibitors used may cease to control cancer. In this situation, doctors may recommend another ALK inhibitor, increase the dose of the current inhibitor, or suggest trying pemetrexed-based chemotherapy (a type of chemotherapy that works particularly well for ALK-positive lung cancers). 

 

Sources:  

Healthline.com 

Medicinenet.com 

Lung.org 

Lcfamerica.org 

Alkpositive.org 

 

ROS1 and Cancer 

Physicians can tell what form of cancer a tumor is by looking at it under a microscope. Physicians can also test for mutations in the tumor’s DNA that could be causing it to grow. These changes are sometimes referred to as biomarkers or molecular markers. 

One way to look at it is that our DNA is a set of instructions. If the instruction manual contains a typo, the cell will receive incorrect instructions and may develop cancer. Biomarker testing looks for those mistakes, letting doctors know if you’re a candidate for a targeted medication that treats those errors directly. 

An error in the ROS1 gene is one biomarker that physicians look for in non-small cell lung cancer. If you have non-small cell lung cancer, it is important to talk to your doctor about comprehensive biomarker testing to see if you have an error in the ROS1 gene or another biomarker. The results of this testing influence your treatment options. 

What Is the ROS1 Gene? 

In ROS1-positive lung cancer patients, part of the ROS1 gene fuses (joins) with another gene. This causes uncontrolled cell growth and cancer by activating the ROS1 gene. A ROS1 fusion or ROS1 rearrangement is the name for this gene alteration. The ROS1 gene can join forces with a variety of other genes. The CD74 gene is the most common cause of lung cancer. A patient is termed to be ROS1-positive when ROS1 fuses or unites with another gene and produces lung cancer. At this time, regardless of the type of ROS1 rearrangement you have, the recommended course of treatment for individuals who are ROS1-positive is the same. 

How do you know if you have ROS1-positive lung cancer? 

To determine if your lung cancer is ROS1-positive, you need to test the tumor tissue or your blood. There are several different types of tests that doctors use. 

• FISH analysis: looks at changes in the chromosomes through tissue under a microscope 
• Immunohistochemistry: looks for proteins in the cell under a microscope 
• Next-generation sequencing (or comprehensive biomarker testing): tissue from a patient’s tumor (gathered from a biopsy) is placed in a machine that looks for a large number of possible biomarkers at one time 
• Liquid biopsy: looks for tumor DNA in the blood 

Your doctor may perform several of these tests at the same time to help confirm the results. 

What Is ROS1-positive lung cancer? 

Any lung cancer that tests positive for a fusion in the ROS1 gene is referred to as a ROS1-positive lung cancer, also known as a ROS1 rearrangement in lung cancer. About 1-2 percent of patients with non-small cell lung cancer (NSCLC) had ROS1 rearrangements. Lung cancer that is ROS1-positive is more aggressive and can spread to the brain and bones. 

When the ROS1 gene combines with another gene, it results in ROS1-positive lung cancer. The ROS1 gene is trapped in the “on” position as a result of this fusion. Cancer is caused by quick cell growth, which is “driven” by this. The ROS1 gene is a receptor tyrosine kinase, a cell surface receptor that has been proven to be not just a critical regulator of normal cellular activities, but also a crucial regulator of cancerous processes. 

ROS1 is an oncogene. An oncogene, according to the National Cancer Institute, is a gene that is normally involved in cell growth but turns cancerous when a mutation occurs.  

What are the risk groups for ROS1-positive lung cancer? 

Studies have found that certain factors are associated with ROS1-positive lung cancer: 

The ROS1 gene is altered in about 1-2 percent of lung cancer patients and generally appears in adenocarcinoma non-small cell lung cancer. Patients who are ROS1-positive tend to be younger than the average lung cancer patient and have little to no smoking history. 

• Age: The median age of people with ROS1 rearrangements is estimated to be 50.5. (The median age for lung cancer, in general, is 72.) 
• Sex: ROS1 seems to be more common in females, with 64.5 percent of occurrences in one study. (Lung cancer, in general, is more common in male patients.) 
• Smoking history: A more significant percentage—an estimated 67.7 percent—are never-smokers. (Smokers are at greater risk for lung cancer overall.) 

Treatment options for ROS1-positive lung cancer 

Knowing if you have ROS1-positive lung cancer is important no matter your stage of lung cancer but has the most treatment implications for stage four patients. 

First-line Treatment 

Patients with stage four ROS1-positive lung cancer will likely be prescribed a pill called a ROS1 tyrosine kinase inhibitor (TKI) or ROS1 inhibitor. There are currently two FDA-approved options: crizotinib or entrectinib. 

Second-line Treatment 

The cancer is likely to progress in a few months to years, and the ROS1 inhibitor may become ineffective. A novel resistant mutation will occur in some people. To rule out this possibility, your doctor may perform a tissue or liquid biopsy. When a patient develops resistance to a ROS1 inhibitor, your doctor may suggest a clinical study or the use of an off-label targeted medication. This suggests that it is approved to treat a distinct biomarker, but not ROS1. If a patient has been treated with crizotinib and the disease has spread only to the brain, your doctor may recommend entrectinib, which can treat brain tumors. Other treatments may be used to treat cancer that has spread to the brain. 

Third-line Treatment 

If the cancer continues to grow after second-line treatment, the next option will include a clinical trial, chemotherapy with or without a ROS1 inhibitor, or chemotherapy with or without immunotherapy. 

Work with your doctor to discuss your goals and options each time you must make a treatment decision. The three big questions to ask are: 

• What is the goal of this treatment? 
• What are the potential side effects? 
• What other options do I have? 

Research is happening quickly, with clinicals trials actively enrolling ROS1-positive patients now.  

 

Sources:  

https://www.verywellhealth.com 

https://lcfamerica.org 

https://www.lung.org 

HER2 and Cancer 

HER2 (human epidermal growth factor receptor 2) is a gene that was discovered in the 1980’s by researchers who determined the presence of too many HER2 proteins, which this gene makes, can cause cancer to grow and spread at an increased rate. Today, researchers are still researching how to slow or alter the growth of these types of cells. 

HER2 proteins are found on the surface of breast cells. They’re involved in normal cell growth but can become overexpressed, meaning the levels of the protein are higher than normal. 

What Is the HER2 Gene? 

Including HER2, genes are responsible for creating different proteins for cells to maintain their health and function properly. Some of these genes and the proteins they make can influence how diseases such as cancer develop and respond to treatment. To determine whether these genes are present that affect your cancer, doctors will remove a sample of tissue from the tumor and test to see which genes or proteins are abnormal within the cancer cells. 

The HER2 gene makes HER2 proteins, which are receptors on breast cancer cells and present in various other cancers. In normal and healthy cells, HER2 receptors maintain cell growth, division, and cellular repair. In an estimated 10 to 20 percent of breast cancer patients, the HER2 gene is abnormal, and too many copies of itself are made. This leads to cancer cells growing, dividing, and spreading at an increased rate within the body. 

What Does HER2-Positive Mean? 

Cancers that are considered HER2-positive refer to tumors that have cancer cells with HER2 proteins present. Enough of these proteins are present that the drugs and therapies developed in clinical trials for HER2-positive cancers will likely be effective for treatment. The two most common testing methods to determine the status of HER2 in cancer are: 

Immunohistochemistry (IHC) test: in the IHC test, a chemical dye is used to stain any present HER2 proteins. The amount of HER2 proteins that are stained are used to determine the results of the test, which are given a score of 0 to 3+. 0 to 1+ is considered HER2-negative. If the score is 2+, it is considered borderline and additional testing may be needed. A score of 3+ is considered HER2-positive and it is likely the tumor will respond to a targeted therapy. 

Fluorescence In Situ Hybridization (FISH) test: The FISH test utilizes labels chemicals that bind to proteins in the body. When they are attached to HER2 proteins, the chemicals cause the label to glow in the dark. This testing method is the most accurate, but results take longer and cost more money so this testing method is often used after the HER2 status is already suspected to be positive.  

In most cases, cancers with testing results of IHC 3+ or FISH positive respond to drugs and therapies that target HER2-positive cancers. An IHC 2+ test result is considered borderline. With an IHC 2+ result, the tissue should be retested with the FISH test. 

What Is a HER2-Positive Breast Cancer? 

For breast cancer and other HER2-positive cancers, the prognosis is often worse but thanks to HER2 inhibitors developed in clinical trials, the survival rate and quality of life in patients with HER-positive breast cancer have increased. 

When cancer has the HER2 gene amplification or HER2 protein overexpression, it is referred to as HER2-positive in the pathology report. These cancers often grow faster, are more susceptible to spreading throughout the body, and are more likely to recur after remission than HER2-negative cancers. 

What Are HER2 Inhibitors? 

Despite HER2-positive cancers being more aggressive than those without the presence of HER2, HER2 inhibitors can treat HER2-positive cancers more effectively than standard treatments such as chemotherapies and radiation therapy. Inhibitors are a class of medicines that treat all stages of HER2-positive cancer, from early-stage to metastatic. HER2 inhibitors are also called anti-HER2 therapies and HER2-targeted therapies. They can detect, locate, and bind to HER2 proteins in cancer cells and prevent them from performing vital cell functions, and kill them. 

HER2 inhibitors in breast cancer have caused survival rates and quality of life to improve in patients. For other types of cancer that are HER2-positive, research on new drugs is still ongoing in clinical trials, which are available to patients with HER2-positive cancer. 

What Are the Treatment Options for HER2-Positive Breast Cancer? 

Once receiving testing results indicating a HER2 mutation is present in the cancer cells, your doctor will use this to plan treatment. This may include one of the following: 

• Trastuzumab (Herceptin): This is the most common drug, is often used with chemotherapy, and improves the outlook of HER2-positive breast cancer and results in a longer lasting remission. This drug is administered intravenously and is considered a type of biologic therapy. Treatment typically lasts one year, and follow-up appointments will be scheduled for another two years to monitor the patient. 
• Herceptin biosimilars: These drugs are reverse engineered to produce similar effects to biologic therapies. The FDA has approved five Herceptin biosimilars, including trastuzumab-dkst (Ogivri) and trastuzumab-qyyp (Trazimera). 
• Trastuzumab/hyaluronidase-oysk (Herceptin Hylecta): In 2019, the FDA approved Herceptin Hylecta, an injectable medication that is administered more quickly than herceptin. Cardiac monitoring is also required. 
• Pertuzumab (Perjeta): This drug may be used in conjunction with Herceptin for HER2-positive breast cancers with a high risk of recurrence (stage 2 and above), or for cancers that have spread to the lymph nodes. 
• Neratinib (Nerlynx): This drug can be recommended for cancer treatment with Herceptin is complete for patients with a higher risk of recurrence. 
• Margetuximab-cmkb (Margenza): This new HER2 drug is used to treat advanced or metastatic breast cancer in people who have already received two previous HER2 treatments. 

What Other Types of Cancer Can Have HER2 mutations? 

Breast cancer is known as the most common cancer seen to be HER2-positive. However, HER2 mutations also occur in bladder, pancreatic, ovarian, and stomach cancers. 

These HER2-positice cancers may also be called c-erbB-2 positive and human epidermal growth factor receptor 2-positive. 

Difference Between HER2-Positive and HER2-Negative Breast Cancer 

The main differences in HER2-negative and HER2-positive breast cancer are how the cancer is treated and how aggressive it is. Treatment for HER2-positive cancer includes inhibitors to prevent those abnormal proteins and cells from surviving, while avoiding healthy cells. Treatment for HER2-negative cancer isn’t targeted and may also affect healthy cells in addition to killing cancer cells. This often leads to more side effects than in targeted therapies. 

Medications that may be used for HER2-negative breast cancer include: 

• sacituzumab govitecan (Trodelvy), an IV treatment 
• talazoparib (Talzenna) 
• abemaciclib (Verzenio) 
• alpelisib (Piqray) 
• everolimus (Afinitor) 
• olaparib (Lynparza) 
• palbociclib (Ibrance) 
• ribociclib (Kisqali) 

Patients with HER2-positive cancer of any type may also be eligible for cancer clinical trials that treat HER2-positive patients. While there is other inclusion criteria for each trial, you are unable to enroll without testing results showing the presence of a HER2 mutation.  

Sources: 

https://www.breastcancer.org 

https://www.healthline.com 

NRG1 and Cancer 

Epidermal growth factor (EGF) is a protein that stimulates cell growth, proliferation, and differentiation of cells into various tissues. Neuregulin 1 (NRG1) is a gene that belongs to the EGF family and plays a vital role in the development of the peripheral nervous, heart, and gastrointestinal tissues as well as the repairing process. NRG1 is considered a promising biomarker, and its association with cancer is through its mutation and fusion. Due to its potential for targeted therapies, NRG1 mutations and fusions are intensely researched. 

What is NRG1 Mutation? 

A mutation is defined as a permanent and structural change or damage in the DNA or the RNA, and it changes the message the gene conveys. NRG1 mutation is where the neuregulin 1 gene is damaged by alteration and starts taking the cancerous cell in its body. NRG1 mutations are most seen in lung cancer and breast cancer patients. As NRG1 is mainly responsible for cell growth, proliferation, and differentiation, the mutation it goes through is called oncologic driver mutation in medicine. The driver mutations help the medical teams design a treatment strategy that can stop cancer cells from growing, so more and more medical professionals are checking the tumor tissues for driver mutations before starting treatment. 

What is NRG1 Fusion? 

NRG1 is mostly associated with lung cancer but according to an article published in the Medical Library of Medicine, NRG1 fusions have been identified in several types of cancer. And what is gene fusions? They are hybrid genes that are created as a result of DNA rearrangements. When the fusion occurs in an oncogenic gene, it messes the regular activities and acts as a driver of starting and preserving the cancerous cells. The tumors containing NRG1 fusion include pancreatic ductal adenocarcinoma, colorectal, breast, thyroid, squamous cell carcinomas, ovarian, gastrointestinal stromal tumors, renal cell carcinomas, cholangiocarcinoma, bladder, ovarian, neuroendocrine and sarcoma cancers. 

What is NRG1 Fusion Lung Cancer? 

A type of NRG1 fusion named CD74-NRG1 is common among patients suffering from invasive mucinous adenocarcinomas of the lung. There are also other NRG1 fusion partners, such as ATP1B1, SDC4, and RBPMS, that have been found in lung cancer patients. About 20 percent of NRG1 fusion-positive non-small cell lung cancer patients are classified as non-mucinous adenocarcinomas. 

NRG1 Fusions in Solid Tumors 

A solid tumor is an irregularly grown tissue that generally does not accommodate liquid areas or cysts. They can be cancerous or noncancerous in nature. Their classification is based on the cell types that create them, such as sarcomas, lymphomas, and carcinomas. According to recent studies, NRG1 fusions are mostly seen in cholangiocarcinoma, pancreatic ductal adenocarcinoma, renal cell carcinoma, and ovarian cancer, respectively. 

What is NRG1 Fusion Pancreatic Cancer? 

NRG1 fusion pancreatic cancer is the most common type of cancer that NRG1 fusion is seen in. The clinical trials targeting the NRG1 fusion are providing promising results such as shrinking tumor size, especially in solid tumors. If you would like to learn more about clinical trials focusing on pancreatic cancer, feel free to explore your options from all over the world. 

 

Source: 

sciencedirect.com 

ncbi.nlm.nih.gov 

cancer.gov 

targetedonc.com 

medpagetoday.com 

MET and Cancer 

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Most patients with NSCLC are diagnosed at an advanced stage, and conventional chemotherapy and radiotherapy have shown limited efficacy in treatment. In recent clinical studies, many drugs targeting MET have been a promising treatment strategy for NSCLC. 

What Is MET? 

MET (Mesenchymal epithelial transition) is a type of protein-making gene that sends signals within cells and plays a role in the growth and survival of cells. Mutated (altered) forms of the MET gene can cause abnormal cells to grow and spread throughout the body. MET gene mutations can be seen in liver, head, neck, and lung cancer. 

What Is the MET Mutation in Lung Cancer? 

A particular error in MET, called exon 14 skipping, has the most impact on lung cancer therapy. Proteins in the cell must be broken down and removed from the body after meeting the protein need. Otherwise, they accumulate and cause problems in the cell. When the MET protein is no longer needed, a protein called CBL helps break it down. Where CBL joins with MET, it is encoded by a portion of the MET gene, called exon 14. Mutations in the MET gene that cause exon 14 removals (or omission) prevent CBL from binding. This allows the MET protein to stay longer and send growth signals that can promote cancer. About 5 percent of lung cancer patients have MET exon 14 skipping present. 

What Is the MET Amplification? 

Having extra copies of the MET gene in the body is called MET gene amplification. Because MET is a growth receptor, additional copies of the MET gene mean extra growth signals are sent to tumor. Having extra copies of the MET gene in lung cancer is not uncommon, but an amplification of MET is an essential biomarker for some patients. If there are multiple copies of the MET gene, the patient may respond better to MET-targeted therapy. MET amplification can be detected via next-generation sequencing (NGS). Still, in some cases, a particular test called FISH (looks for gene changes in cells) can be used to calculate the number of extra copies of MET in cancer cells. 

What Is The MET Mutation in Non-Small Cell Lung Cancer? 

Doctors look for duplications or errors in the MET gene when diagnosing non-small cell lung cancer because MET changes are primarily seen in adenocarcinoma NSCLC. Several preclinical and clinical studies have been conducted on many drugs targeting MET. Preclinical and clinical studies have suggested that MET activation is a secondary driver of acquired resistance to targeted therapy in subpopulations. Therefore, agents targeting c-MET (C-mesenchymal-epithelial transition factor) are a promising treatment strategy for NSCLC. In preclinical and clinical trials, c-MET inhibitors have shown some antitumor activity in NSCLC. The MET/HGF (hepatocyte growth factor) axis is a promising therapeutic target in advanced NSCLC. MET/HGF overexpression and MET gene alterations provide many potential biomarkers in lung cancer. 

 

Sources: 

Ncbi.nlm.nih.gov 

Ascopubs.org 

Nejm.org 

Lung.org 

Sciencedirect.com 

 

JAK2 and Cancer 

It helps to have a basic understanding of how genes and enzymes interact in our body to better understand the JAK2 gene and enzyme’s association with cancer. 

Our genes are the blueprints or instructions for how our bodies work. Every cell in our body contains a collection of these instructions. They instruct our cells on how to produce proteins, which in turn produce enzymes. 

Enzymes and proteins send messages to other regions of the body to accomplish specific functions, such as aiding digestion, stimulating cell growth, and protecting us from infections. 

Our genes within the cells can become mutated as our cells develop and divide. Every cell that the cell produces inherits the mutation. When a gene is mutated, the blueprints can become difficult to read. 

Sometimes the mutation results in an error that is so difficult to interpret that the cell is unable to produce any protein. Other instances, the mutation causes the protein to work extra hours or stay turned on all the time. When a mutation impairs the function of proteins and enzymes in the body, it can result in disease. 

What Is JAK2? 

Our cells receive instructions from the JAK2 gene to produce the JAK2 protein, which promotes cell development. The JAK2 gene and enzyme are essential for regulating cell growth and production. 

They’re very vital for blood cell growth and formation. In our bone marrow stem cells, the JAK2 enzyme is hard at work. These cells, also known as hematopoietic stem cells, are in charge of producing new blood cells. 

What Is the Function of JAK2? 

The JAK2 enzyme is always turned on due to mutations prevalent in people with myelofibrosis (MF). This indicates that the JAK2 enzyme is continually active, resulting in megakaryocyte overproduction. 

Other cells are told to release collagen by these megakaryocytes. As a result, scar tissue develops in the bone marrow, which is a clear symptom of MF. 

Other blood diseases have been associated to JAK2 mutations. The mutations are usually associated with a disorder known as polycythemia vera (PV). The JAK2 mutation results in unregulated blood cell production in PV patients. 

Around 10 to 15 percent of people with PV will go on to develop MF. Researchers don’t know what causes some people with JAK2 mutations to develop MF while others develop PV instead. 

What Drugs Are JAK Inhibitors? 

JAK2 mutations have been detected in more than half of people with MF and more than 90 percent of those with PV, thus it’s been the focus of a lot of research. 

There is just one FDA-approved medication that targets JAK2 enzymes: ruxolitinib (Jakafi). This medicine works as a JAK inhibitor, which means it inhibits JAK2 activity. 

The enzyme isn’t always turned on when the activity of the enzyme is slowed. This reduces megakaryocyte and collagen production, reducing the formation of scar tissue in MF. 

The drug ruxolitinib also regulates the production of blood cells. It does this by slowing the function of JAK2 in hematopoietic stem cells. This makes it helpful in both PV and MF. 

Currently, there are many clinical trials focusing on other JAK inhibitors. Researchers are also working on how to manipulate this gene and enzyme to hopefully find a better treatment or a cure for MF. 

JAK2 and Its Role in Myelofibrosis 

JAK2 was discovered 30 years ago in a search for anything approximating a family of enzymes known to stimulate cell growth and development at the time. JAK2 was discovered in a line of eternally youthful cells that give rise to blood cells.  In a mouse model, for example, removing the JAK2 gene causes the mouse to be unable to make enough blood cells and die. 

Since then, a lot more has been learned about its involvement in blood cell development. In 2005, researchers discovered that roughly half of myelofibrosis patients had a JAK2 mutation known as V617F. They also discovered that people with the V617F mutation did not live as long after being diagnosed as individuals who did not have the genetic mutation. 

The V617F mutation is by far the most common mutation seen in myelofibrosis.  JAK2 molecular testing has become standard in the work up and diagnosis of myelofibrosis and other myeloproliferative diseases. 

JAK2-Positive Polycythemia Vera 

Polycythemia vera (PV) is a chronic, progressive myeloproliferative neoplasm (MPN) characterized by an increase in the number of red blood cells. PV is more common in men over the age of 60, but it can affect anyone. A raised leukocyte (white blood cell) count, an elevated platelet count, and an enlarged spleen are common in PV patients, especially with time. 

It is unknown what causes PV and other myeloproliferative neoplasms (MPNs). PV and other MPNs, however, may be caused by non-inherited genetic changes affecting proteins involved in cell signaling pathways. 

Nearly all PV patients have a mutation called “JAK2V617F” (found in the JAK2 gene) in their blood-forming cells. This mutation is one of the ways that JAK (Janus kinase) pathway signaling can become dysregulated and cause the body to produce too many blood cells. 

JAK2 Mutations in Myeloproliferative Disorders 

Normal JAK2 gene variants create an enzyme that controls the formation of blood cells. Blood cell production is consistently boosted when this gene is mutated. 

A JAK2 mutation can cause a variety of myeloproliferative illnesses, including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, depending on which cells are activated. 

Platelet production is triggered by a mutation in the calreticulin (CALR) gene, which causes essential thrombocythemia and primary myelofibrosis. Mutations in thrombopoietin receptor (MPL), a proto-oncogene, can raise the risk of essential thrombocythemia or primary myelofibrosis. 

 

Sources:  

https://www.mpnresearchfoundation.org 

https://nyulangone.org 

https://www.bms.com 

PIK3CA and Cancer 

PIK3CA, or Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha is a gene that encodes p110, a protein responsible for the proliferation, growth, differentiation, motility, and survival of cells. PIK3CA is a component of the P13K/AKT/mTOR pathway, which is involved in a variety of cell growth processes.  

Certain people may have mutations in this gene. Once the mutation occurs in PIK3CA genes, abnormal p110 proteins are created at an increased rate. PIK3CA gene mutations cause cells to grow uncontrollably, which can develop into cancer.  

The PIK3CA gene mutation can be found in many cancers, but most often is found in the following cancer types: 

• Breast cancer 
• Ovarian cancer 
• Colorectal cancer 
• Lung cancer 
• Stomach (gastric) cancer 
• Brain cancer 

What Is the PIK3CA gene mutation? 

When mutations occur in PIK3CA and develop into cancer, the mutation helps the cancer cells avoid death (apoptosis), change its metabolism, and improve its ability to break away and move to other areas of the body (metastasize). Due to the overproduction of these proteins, cases of PIK3CA-positive cancer are typically more aggressive and have a worse prognosis than cancers without the gene mutation present.  

PIK3 mutations are classified as “driver mutations” meaning the proteins created with the mutation fuel the cell’s growth and leads to the spread of cancer. Although the disease is more aggressive with mutations such as PIK3CA present in the cancer cells, targeted therapies have been developed to target and kill cancer cells with specific alterations, which have improved survival rates and quality of life for patients. 

Are PIK3CA Mutations Hereditary? 

Although some gene mutations seen in cancer are inherited from your family, the PIK3CA mutation is not hereditary. Therefore, anyone who has this gene mutation developed it over the course of their lifetime from a cause that is still unknown to researchers.  

Mutations in PIK3CA are considered somatic, meaning they developed at some point during your lifetime instead of being inherited from family. This can lead to a variety of illnesses during embryonic development that are not cancer, including enlarged fingers, legs, or blood vessels. Surprisingly, those with these overgrowth conditions are not at a higher risk of cancer. Benign skin disorders such as seborrheic keratoses have been linked to PIK3CA mutations.  

What Cancers Have PIK3CA Mutations? 

Many cancers can test positive for a PIK3CA gene mutation, however, as mentioned earlier, they are typically seen in breast cancer, ovarian cancer, colorectal cancer, lung cancer, stomach (gastric) cancer, and brain cancer. 

To test for mutations in the PIK3ca gene, doctors will perform a test called therascreen, which was FDA-authorized in 2019 to detect mutations in PIK3CA. A sample of your blood or tumor tissue is used in the test. The blood test is performed in the same way as any other blood test. A needle will be used to draw blood from your arm by a nurse or technician. The sample is collected and sent to a facility for analysis. In breast tumors, modest amounts of DNA are released into the bloodstream, so a blood sample will be tested for the PIK3CA gene rather than the tumor tissue.  

If you get a negative result on the blood test, you should have a biopsy to confirm it. Your doctor will remove a sample of tissue from the tumor through a minor procedure. The tissue sample then goes to a lab, where technicians test it for the presence of the PIK3CA gene mutation. 

How Common Is the PIK3CA mutation? 

PIK3CA mutations are common compared to other solid tumor mutations, but vary depending on which disease type they are found in. Read more below for the most common tumor types observed with PIK3CA mutations. 

Mutation of the PIK3CA Gene in Breast Cancer 

Doctors will test for mutations of the PIK3CA gene in patients with breast cancers, but especially if they are ER-positive, HER2-negative breast cancer. Roughly 30 to 40 percent of these cancers test positive for a PIK3CA gene mutation.  

Breast cancer with PIK3CA is treated with Alpelisib, a targeted drug that is a PIK3 inhibitor and is often combined with fulvestrant, a hormone drug that treats advanced hormone receptor-positive breast cancer in postmenopausal women. Before receiving this treatment, doctors will perform PIK3CA gene mutation test to confirm the presence the abnormal proteins. In cancer treatment, inhibitors are artificially made substances that prevent vital functions from being performed in proteins or cells with specific alterations or mutations such as PIK3CA. This leads to cancer cells being unable to grow or spread, and eventually their death. 

In clinical trials, PIK3CA mutated breast cancer patients on alpelisib showed an average of 11 months progression free survival compared to 5.5 months progression free survival without alpelisib. 

Mutation of the PIK3CA Gene in Ovarian Cancer 

In ovarian cancers, PIK3CA mutations are detected in over 30 percent of all tumors, and 45 percent of ovarian tumors with the endometroid and clear cell subtypes. 

In ovarian cancers, the PI3K/AKT/mTOR is one of the most investigated intracellular signaling pathways. A dis-regulation of this pathway has been shown in several different tumor types, including ovarian cancers. For these tumors, mTor proteins are a potential target for inhibitors, which could ultimately play a pivotal role in counteracting cellular proliferation, leading to the death of cancer cells. 

Promising mTor inhibitors being studied in clinical trials for PIK3CA-positive ovarian cancer are temsirolimus, everolimus, and ridaforolimus. 

Mutation of the PIK3CA Gene in Colorectal Cancer 

In colorectal cancer (CRC), mutations of PIK3CA have been reported in 10 to 20 percent of tumors. 80 percent of mutations in CRC are found in two hot spots in exon 9 and exon 20, which are DNA sequences in mature messenger RNA that encode the amino acids of proteins. 

According to studies, taking aspirin regularly after a diagnosis of CRC with the presence of PIK3CA mutations has a positive impact on the survival rate in patients. This may be used as an adjuvant therapy along with other PIK3CA inhibitors. 

 

Sources: 

https://www.frontiersin.org 

https://aacrjournals.org 

https://molmed.biomedcentral.com 

https://www.ncbi.nlm.nih.gov 

AKT1 and Cancer 

AKT1, or AKT serine/threonine kinase 1 with its full name, is an oncogene, and gives the instructions for the creation of a protein called AKT1 kinase. AKT1 has many other names such as AKT1_HUMAN, PKB (protein kinase B alpha), proto-oncogene c-Akt, RAC (rac protein kinase alpha), v-akt murine thymoma viral oncogene homolog 1. 

AKT1 kinase, the protein produced upon the instruction of AKT, is vital in terms of signaling pathways and is found in several cells all over the body. Its functions include the regulation of cell growth and proliferation (division), differentiation, survival, and self-destruction (apoptosis). 

According to the research showing the cell-to-cell communication role of AKT1 between the neurons (nerve cells) neuronal survival and the formation of memories, the signaling triggered by this protein is critical for the development of a functional nervous system. Like other oncogenes, when AKT1 goes through a mutation, it may cause the healthy cells to become cancerous. 

What Is AKT1 Gene Mutation? 

Hyperactivation of AKT, which is the most common activated protein kinases in human cancers, might cause irregular growth, proliferation, and apoptosis of cells. 

What Is the Function of AKT1 Gene Mutation? 

The mutation of the AKT1 gene, which is a fundamental element of the signaling pathway, affects numerous processes of tumor formation (tumorigenesis). 

What Are AKT1 Inhibitors? 

As the AKT1 mutation may lead to the formation of tumor, targeting AKT seems to be a solid strategy to fight cancer. There are currently many AKT inhibitors being researched at the clinical development stage. Here are some AKT inhibitors that are being developed and assessed in clinics: 

• AFURESERTIB (GSK2110183) and GSK2141795 
• ARQ 092 and ARQ 751 
• AZD5363 (Astrazeneca) 
• Ipatasertib (GDC-0068) 
• MK-2206 (Merck; MSD) 
• Perifosine 

What Cancers Have an AKT1 Gene Mutation? 

According to the article published in the National Library of Medicine (numbered 32269671) “AKT1 E17K is a recurrent somatic mutation observed in breast cancer, colorectal cancer, lung cancer, and ovarian cancer, that functions mainly to activate the PI3K/Akt signal pathway, and the E17K hotspot is the most characteristic mutation of the AKT1 gene.” There are other studies supporting these findings, showing that the mentioned mutation may lead to protein activation, which eventually leads to cancer. 

Other Health Conditions Related to the AKT1 Mutation 

In addition to cancer, the AKT1 mutation may cause various other health conditions. These conditions include the below listed: 

Proteus syndrome: It is a rare condition where the patient’s bones, skin, and other tissues irregularly grow. Not an inherited condition, it starts after birth and becomes more severe as the patient grows. The disproportionate and asymmetrical growth of organs and tissues is a result of the AKT1 gene mutation. 

Cowden syndrome: Also called multiple hamartoma syndrome, might develop through inheritance and as well as a new mutation. It is defined as a genetic disorder that causes the development of both benign and cancerous tumors. The types of cancer associated with Cowden syndrome are the skin, thyroid, breast, endometrium, kidney, and colorectal cancer.  

Schizophrenia: Studies show that the gene that is suspected to cause schizophrenia affects the AKT signaling. In addition, the variations (called the polymorphisms) in the AKT1 gene have also been associated with the disease in terms of lowered protein expressions in schizophrenia patients’ brains. 

 

Sources: 

medlineplus.gov 

genentechoncology.com 

sciencedirect.com 

cancer.net 

C-MET and Cancer 

Small cell lung cancer is a type of cancer characterized by small, blue, and malignant (malignant) cells that are about twice the size of lymphocytes and accounts for 15 percent of all lung cancers. Clinical trials have shown that c-MET inhibitors are a promising treatment modality for non-small cell lung cancer (NSCLC). This article includes the effects of the c-MET gene on small cell lung cancer and other cancer types.   

What is C-MET Gene? 

C-MET, also called tyrosine-protein kinase (enzyme) MET or hepatocyte growth factor receptor (HGFR), is a protein encoded by the mesenchymal-epithelial transition (MET) gene in humans. MET is a single-pass tyrosine kinase receptor required for embryonic development, organogenesis, and wound healing. Mutated forms of the MET gene can cause abnormal cells to grow and spread throughout the body. MET mutation is often detected by DNA-based sequencing and PCR methods. 

What Is C-MET in Cancer? 

C-MET supports cancer cell growth and proliferation. Abnormal activation of c-MET increases the risk of kidney cancer, an inherited condition called hereditary papillary renal carcinoma (HPRC). It can also promote the development and progression of cancers such as breast, liver, gastrointestinal, stomach, ovarian, lung, colon, prostate, and pancreatic carcinomas. 

Where Is C-MET Found? 

The c-MET proto-oncogene is located on chromosome 7 (7q21-31). Chromosome 7 encompasses approximately 159 million DNA building blocks (base pairs) and represents more than 5 percent of the total DNA in cells. Chromosome 7 likely contains 1,000 to 1,400 genes that provide instructions for making proteins. Many types of cancer are associated with damage to chromosome 7. 

What Does C-MET Stand For? 

A proto-oncogene active in cell signaling, c-MET promotes the growth and proliferation of cancer cells. C-MET protein overexpression occurs in 25-75 percent of non-small cell lung cancer and is associated with a poor prognosis of NSCLC. 

  

C-MET Inhibitors in The Treatment of Lung Cancer 

Doctors look for changes in the MET gene when diagnosing non-small cell lung cancer. In clinical trials, agents targeting c-MET are a promising treatment strategy for NSCLC. In addition, c-MET inhibitors have shown some antitumor activity in NSCLC. 

In recent years, a small molecule c-MET inhibitor has been developed that can be used as monotherapy or in combination with other agents. Of these, cabozantinib (Cabometyx® and Cometriq®, Exelixis Inc., San Francisco, USA) and crizotinib (Xalkori®, Pfizer, New York, USA) are approved by the US Food and Drug Administration (FDA), and the European Medicines Agency (EMA) has received.

Massive Bio specializes in finding advanced clinical treatments for each type of cancer. We’re here to help you match our SYNERGY Artificial Intelligence (AI) platform to the most appropriate clinical trial for your cancer type and current stage of the disease. If you don’t know which clinical trial is best for you, that’s okay. Let’s explore it together. 

 

Sources: 

Medlineplus 

Deepdyve 

Pubmed.ncbi.nlm.nih.gov 

Pubmed.ncbi.nlm.nih.gov 

Springer 

Pvillage 

PD-L1 and Cancer 

PDL1 is a protein that prevents immune cells in the body from attacking non-harmful cells. The immune system is designed to combat alien things such as viruses and bacteria, not your own healthy cells. PDL1 is abundant in certain cancer cells. This permits cancer cells to “fool” the immune system into thinking they’re alien, dangerous molecules. 

If your cancer cells have elevated levels of PDL1, you might be able to benefit from immunotherapy. Immunotherapy is a treatment that helps your immune system detect and destroy cancer cells by boosting them. Immunotherapy has shown to be quite beneficial in the treatment of some malignancies. It also has fewer negative effects than most other cancer treatments. 

What Is PD-L1? 

A protein that works as a stopping mechanism on the immune system to keep it under control. On certain normal cells, PD-L1 can be found in higher-than-normal numbers, and on some cancer cells, it can be found in higher-than-normal amounts. When PD-L1 attaches to another protein called PD-1 (present on T cells), it prevents T cells from destroying cells that have PD-L1, including cancer cells. Immune checkpoint inhibitors are anticancer medications that bind to PD-L1 and prevent it from binding to PD-1. The immune system’s “brakes” are released, allowing T cells to attack cancer cells. 

What Is PD-L1 in Lung Cancer? 

All new lung cancer patients should have their PD-L1 levels evaluated at the time of diagnosis. This entails utilizing immunohistochemical staining to examine tumor tissue under a microscope. The percentage of cells in a tumor that “express” PD-L1 is determined by a PD-L1 test. Checkpoint inhibitors are a type of immunotherapy drug that may work especially effectively in tumors that express a lot of PD-L1 (50 percent or more). 

If you haven’t had your PD-L1 levels checked, talk to your doctor about whether it’s a good idea. 

What Drugs are PD-L1 inhibitors? 

PD-1 inhibitors and PD-L1 inhibitors are anticancer checkpoint inhibitors that impede the action of the immune checkpoint proteins PD-1 and PDL1 on the cell surface. Immune checkpoint inhibitors are becoming popular therapy for various cancer types.  

Immunotherapy using these immune checkpoint inhibitors appears to decrease tumors in a greater number of patients and across a wider spectrum of tumor types, with lower toxicity levels and longer-lasting responses than conventional immunotherapies. For a variety of malignancies, PD-L1 inhibitors are thought to be the most promising therapeutic class. 

PD-1/PD-L1 inhibitors do not work for all people. The Food and Drug Administration (FDA) has authorized a number of tests that assess the amount of PD-L1 expressed by tumor cells in order to forecast the chance of a cancer recurrence.  

PD-1 inhibitors 

Examples of drugs that target PD-1 include: 

• Pembrolizumab (Keytruda) 
• Nivolumab (Opdivo) 
• Cemiplimab (Libtayo) 
• PD-L1 inhibitors 

PD-L1 inhibitors 

Examples of drugs that target PD-L1 include: 

• Atezolizumab (Tecentriq) 
• Avelumab (Bavencio) 
• Durvalumab (Imfinzi) 
• Both PD-1 and PD-L1 inhibitors have shown to be helpful in treating many different types of cancer. 

Sources: 

https://www.sciencedirect.com 

https://www.ncbi.nlm.nih.gov 

https://oncologypro.esmo.org 

FGFR and Cancer 

The fibroblast growth factor receptors (FGFR) are located on the surfaces of cells which external molecules bind to. For healthy cells, growth factor receptors are responsible for allowing cells to reproduce. If the gene is mutated, changes occur in the signaling of the receptor therefore cancerous cells can develop and reproduce instead of healthy cells. 

There are 4 types of FGFRs and a total of 22 fibroblast growth factors (FGF) that bind to them. Amplifications can occur for any of FGFR1, FGFR2, FGFR3, and FGFR4. Each FGFR can vary in which cancer type is involved, but breast cancer is the most common across the four FGFRs. Although not common, FGFR amplifications can occur in the following cancer types: 

• Breast cancer 
• Bladder cancer 
• Gastric cancer 
• Lung cancer 
• Colon cancer 

What Is the FGFR Mutation? 

Cancer begins with a single or multiple genes within one cell mutate. This mutation is a change that causes an abnormal protein to be produced, or the protein doesn’t get produced at all. Abnormal proteins cause a cell to grow and divide at an uncontrollable rate, eventually causing cancer. 

Deregulated FGFR signaling plays an important role in tumor development and progression in different cancer types. FGFR genomic alterations, including FGFR gene fusions that originate by chromosomal rearrangements, represent a promising therapeutic target. Next-generation-sequencing (NGS) approaches have significantly improved the discovery of FGFR gene fusions and their detection in clinical samples. A variety of FGFR inhibitors have been developed, and several studies are trying to evaluate the efficacy of these agents in molecularly selected patients carrying FGFR genomic alterations. 

What Is the Function of FGFR? 

Each FGFR differs in the specific functions of cells they are responsible for; however, they all take part in the growth and division of cells. Therefore, cancers with FGFR mutations typically are more aggressive and have a worse prognosis. 

What Are FGFR Fusions? 

Gene fusions result from chromosomal rearrangements and are the most common form of mutations. Two independent genes are rearranged and form a hybrid gene. FGFR and other gene fusions are used as a diagnostic and prognostic biomarker in cancer. This allows doctors and researchers to better diagnose the patient’s subtype of disease, treat the cancer, and monitor the disease’s progression. 

FGFR Fusions in Cancer 

Treating cancers that are positive for a mutation in one of the FGFRs involves inhibiting the receptors in cancer cells so they can no longer function, and eventually are killed. The exact drug used depends on several factors such as the type of cancer and biomarker status. The first Food and Drug Administration (FDA) approved therapy for FGFR mutations in bladder cancer was erdafitinib (Balversa) in 2019. Since then, additional therapies are being studied for FGFR mutations in other cancer types. 

Treatments available in breast cancer FGFR clinical trials include targeted therapies such as: 

• TAS120 
• Debio 1347 
• Dovitinib 
• Ponatinib 
• Lucitanib 
• Ninedenib 
• Pazopanib 

These drugs need to be studied extensively in clinical trials because they tailor cancer treatment to the individual patient. Treating biomarkers and mutations is becoming standard, but enough data needs to prove that the drug is both safe and effective to treat cancer with FGFR mutations. 

How Common Are FGFR Mutations? 

Although FGFR mutations are rare in cancer patients overall, it is more common in certain cancer types than others. It is estimated that somewhere between 5 and 10 percent of all cancers have FGFR mutations present, but that number increases to 10 to 30 percent in urothelial carcinoma and intrahepatic cholangiocarcinoma.  

What Are FGFR Inhibitors? 

To be eligible and enroll in an FGFR clinical trial, patients will need a positive test result from biomarker testing showing an overexpression of FGFR. To test someone for the FGFR amplification, there are several options. In every scenario, a tissue sample of the tumor will be collected by a doctor and sent to a lab for an analysis: 

• Genetic tests specifically for the 4 FGFRs 
• Genetic tests for a larger subset of genes 
• Next Generation Sequencing to test the entire human genome 

All of these methods can be beneficial for cancer patients to determine if the FGFR amplification is present. Talk with your doctor to determine which course of action is right for you. A positive test may mean that the patient is eligible for therapies targeting the FGFRs. In some cases, the FGFR amplification can identify which standard treatments the cancer cells will be resistant to. For example, some FGFR cancer cases have been observed to have a resistance towards chemotherapy, a common treatment for breast cancer. 

Massive Bio specializes in finding clinical trials for all cancer types with the FGFR gene fusion or other gene alterations. If you’ve been diagnosed with any FGFR cancer types or have a tumor that is FGFR fusion-positive, we’re here to help. If you don’t know which subtype of cancer you have, that’s okay. Additional testing can help you determine your exact diagnosis.  

Sources: 

https://www.cancer.net 

https://www.ncbi.nlm.nih.gov 

NRTK and Cancer 

Physicians can tell what form of cancer a tumor is by looking at it under a microscope. However, doctors can check for alterations in the tumor’s DNA that could be causing it to develop. These alterations are sometimes referred to as biomarkers or molecular markers. 

One way to look at it is that our DNA is a set of instructions. If the instruction handbook has a mistake, the cell will get incorrect instructions and may develop cancer. Biomarker testing searches for such mistakes, letting doctors know if you’re a candidate for a targeted medication that treats those errors directly. 

One indicator that doctors check for is an abnormality in the NTRK gene (pronounced en-track). 

A fragment of the Neurotrophic tyrosine receptor kinase (NTRK) gene and a piece of an unrelated gene fuse, or join, together in a tumor with an NTRK gene fusion. This promotes uncontrolled cell proliferation and malignancy by activating the NTRK gene. NTRK gene fusions can be seen in a variety of cancers.  

What Is NTRK? 

When a portion of the chromosome carrying the NTRK gene breaks off and connects with a gene on another chromosome, it is called a mutation (change). TRK fusion proteins are aberrant proteins that result from NTRK gene fusions and may cause cancer cells to proliferate. Some malignancies, including as tumors of the brain, head and neck, thyroid, soft tissue, lung, and colon, have NTRK gene fusions. The fusion of the neurotrophic tyrosine receptor kinase gene is also known as neurotrophic tyrosine receptor kinase gene fusion.  

What are NTRK Fusion-Positive Tumors? 

NTRK fusion-positive tumors have been found in breast, cholangiocarcinoma, colorectal, gynecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma, and thyroid malignancies, among others. 

NTRK is identified in between 1,500 to 5,000 cancer-stricken children, adolescents, and adults each year. However, the incidence of NTRK gene fusions differs amongst various tumor types. 

These fusions have been discovered in pediatric malignancies such as gliomas, melanoma, soft-tissue sarcomas, inflammatory myofibroblastic tumors, congenital infantile fibrosarcoma, and mesoblastic nephroma.   

How are NTRK Fusion-Positive Tumors Identified? 

Biomarker assays, such as next-generation sequencing (NGS), immunohistochemistry (IHC), DNA fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR), are used to detect NTRK gene fusions, just like other cancer biomarkers (PCR). 

Only biomarker testing for NTRK gene fusions can identify persons who could be candidates for medicines that target these genetic changes.   

How are NTRK Fusion-Positive Tumors Treated? 

NTRK fusion-positive tumors may be acceptable for therapy with a targeted drug, independent of the kind of cancer or where it originated, thanks to recent breakthroughs in personalized medicine. This is referred to as a tumor-agnostic therapy strategy. 

For NTRK gene fusions, there are currently two Food and Drug Administration (FDA) approved targeted therapies: entrectinib and larotrectinib. These medications are taken as pills and work by directly targeting or inhibiting the fusion that causes cancer to proliferate. 

One thing to keep in mind is that NTRK gene fusions are not the same as NTRK mutations. Treatments for NTRK fusions are available, but not for mutations. If you have an NTRK fusion and later have an NTRK mutation, you may have generated a resistance mutation, in which case NTRK-inhibitor medications may no longer be effective. In this case, a clinical may be effective.  

How Common Is NTRK? 

NTRK gene fusions are found in around 0.3 percent of all solid tumors. However, the frequency varies depending on the kind of malignancy. In uncommon tumors such as secretory breast carcinoma and mammary analogue secretory carcinoma (MASC) of the salivary gland, their frequency is greater than 90 percent.   

Sources: 

https://www.sciencedirect.com 

https://www.ncbi.nlm.nih.gov 

https://oncologypro.esmo.org 

RET and Cancer 

In every cancer cell, there are thousands of genes that help perform vital functions and send messages within the cell. The DNA contains instructions for a person’s cells and when there is a mistake (mutation), the instructions will now incorrectly create and spread abnormal cells, which may eventually lead to cancer. Biomarker testing locates this exact mistake and gives doctors a better understanding of the tumor and how to treat it. Mutations in genes are also known as rearrangements or alterations. 

Biomarker testing looks at certain genes that are commonly mutated or altered in your cancer type. These biomarkers have several uses such as diagnosing the disease, predicting the prognosis, monitoring the progression of the disease, or they can be a target for cancer drugs that search and attack cells with a specific biomarker present. 

What Is RET? 

RET (RET proto-oncogene) is a gene involved in cell signaling to produce the RET protein. This protein is located on the inside and outside of the cell, covering the cell membrane, allowing specific factors to receive signals helping with response to the cell’s environment. 

The RET protein helps develop nerve cells in the intestines and the autonomic nervous system, which is responsible for involuntary body functions (heart rate). This protein also has a role in sperm production and the development of the kidneys. Molecules attach to RET proteins, causing alterations in the cell. The cell then divides or grows at an uncontrollable rate to manage specialized functions, leading to RET-positive cancer. 

What Is the Function of RET Gene? 

The RET gene provides instructions in cells to produce proteins responsible for signaling pathways. Signaling is how cells communicate with each other, ensuring bodily functions are working properly. Specifically, nerve cells developing properly rely on the RET gene. 

What Is RET Driven Cancer? 

Cancer begins with the mutation (rearrangement) of one or multiple genes within one cell. This mutation is a change that causes an abnormal protein to be produced, or the protein doesn’t get produced at all. Abnormal proteins cause a cell to grow and divide at an uncontrollable rate, eventually causing cancer. 

RET mutations are considered somatic, meaning they are not inherited through birth, but acquired at some point throughout your life.  

What Is RET Gene Testing? 

Doctors will perform biomarker tests to determine whether your cancer is positive for elevated levels of RET. This type of genetic test analyzes the DNA of cancer cells using tissue from the tumor or blood. 

If biomarker testing hasn’t been performed already, ask your doctor about testing for the RET gene. If this or other gene mutations are present, your doctor can better understand and plan treatment according to your cancer. 

Who Is Most likely to Have a RET Rearrangement? 

Certain cancer types and subtypes are more likely to have RET rearrangements present. The two most common cancer types with RET gene rearrangements are thyroid cancers such as papillary thyroid carcinoma (RET/PC) and medullary thyroid carcinoma, and lung cancer. However, not all patients with these types of cancers will have the biomarker present, which is why it is important to get tested when you are diagnosed with cancer. 

RET can be present in other cancer types, although it is rare and often not examined unless many different biomarkers are being tested for at once. Researchers look to learn more about RET gene rearrangements in clinical research studies including their cause and new ways to treat, diagnose, and test for them. 

RET Inhibitors in Cancer 

Inhibiting the RET gene means blocking it from performing vital cell functions, that currently cause the cell to grow and divide at an increased rate. By locating and binding to the cancer cells with RET present, healthy cells are more likely to be left untouched and, in some cases, lead to fewer side effects than treatments such as chemotherapy and radiation therapy. 

Common RET inhibitors include pralsetinib (Gavreto) and selpercatinib (Retevmo), while other RET inhibitors are being evaluated in clinical trials and are available to patients who are eligible. 

Massive Bio specializes in finding clinical trials for RET-positive cancer patients who have had genomic testing, as well as other testing such as genetic testing, genomic DNA testing, solid tumor testing, gene testing for diseases, genetic sequencing test, genomic profiling, and Next Generation Sequencing (NGS) testing. If you have been diagnosed with RET-positive cancer, we are well-equipped to help you today. Many clinical trials are studying targeted therapies that are designed for RET cancers. Massive Bio recommends NGS testing for patients to help determine an exact diagnosis.  

Sources: 

medlineplus.gov 

www.retevmo.com 

www.cancersupportcommunity.org 

BRAF and Cancer 

Identifying the cause of why a cancerous cell develops in the body is one of the most central quests of scientists. Genetic factors are a major area of focus in this search. Recently, they have attributed extra importance to biomarkers as they started unlocking their relationship with cancer and their effect on the treatment options. BRAF gene is considered a prominent biomarker for certain types of cancer such as melanoma, thyroid, lung, and colorectal. In this article, we will cover the basics of this gene, its mutation, how to get tested for it, and what inhibitors are used to treat BRAF-positive cancer. 

What Is BRAF Gene? 

BRAF gene creates a specific protein, named B-raf, that instructs the cells to reproduce and grow. Based on the functions given through its instruction, it is classified as a proto-oncogene. It is located on chromosome seven and when mutated, leads to abnormalities in the speed and number of cell reproduction. Why is the BRAF gene important? Because when it mutates, the abnormalities might cause development and spread of cancerous cells. Mutated BRAF gene is classified as oncogene as the out of order instructions it gives cause cancer. 

What Is BRAF Mutation? 

It is an unexpected change in the DNA that makes the BRAF gene send cells a continuous instruction to reproduce and grow but not to stop. When the order of instructions coming from this gene does not include a stop code, the cells divide uncontrollably and might eventually form a tumor. Since the BRAF gene’s initial function is to drive cell growth, any mutation regarding it is considered a driver mutation as it “drives” the cancer growth when altered. However, having only a BRAF mutation alone is not enough to the development of cancer, there should be an additional mutation too. 

Although there are various mutations cataloged (about 30 types), the most common type is BRAF (V600E) mutation, which is associated with melanoma, lung adenocarcinoma (non-small cell lung cancer), and colorectal cancer. This specific mutation responds well to targeted therapy, which is why getting tested and finding out what kind of mutation you have is vital. 

So, if you are asking yourself “what does it mean if I have BRAF mutation?”, you can answer this question with an increased likelihood of developing certain types of cancer including melanoma and colorectal cancer. And know that you have promising treatment options to target this mutation. 

What Is the Relationship Between BRAF Mutation and Cancer? 

BRAF gene’s proto-oncogene character turns into oncogene when a mutation occurs. A healthy BRAF gene makes a protein that instructs the cells to reproduce and grow. A mutated BRAF gene, on the other hand, instructs the cells to do the same thing but does it continuously and without an order to stop. This leads to uncontrolled growth and division of cells, which might lead to cancer. 

The types of cancer associated with BRAF mutations include melanoma, non-small cell lung cancer (lung adenocarcinoma), colorectal cancer, hairy cell leukemia, ovarian cancer, non-Hodgkin’s lymphoma, thyroid cancer, and some types of brain cancers. 

Is BRAF Mutation Hereditary? 

Almost all types of BRAF mutations are considered acquired (somatic), which means not hereditary but developed after birth. This means BRAF mutations cannot be passed down to the following generations genetically. 

How Do I Get Tested for a BRAF Mutation? 

Biomarker testing is not only important for patients whose BRAF mutations are identified, but also for those that do not have any. It provides vital information to design a successful treatment. There are various methods of tests for BRAF mutations. 

Genetic testing: To investigate the DNA of the tumor, a sample of it is collected with a biopsy and sent to the lab for analysis. The lab results prove if you have BRAF mutations or not, and what particular type. In order to perform this test, a biopsy should be possible. 

Blood test: Preferred when a biopsy is not possible. With this method, only certain types of BRAF mutations can be identified, and with less detail compared to genetic testing. 

What are BRAF Inhibitors? 

BRAF inhibitors are medicines that target the mutated BRAF gene and suppress its functions. They do not aim to eliminate cancer like chemotherapy drugs but decelerate tumor growth for a limited period. 

Drugs such as dabrafenib, encorafenib and vemurafenib have been approved as BRAF inhibitors. 

Combined therapy: To diminish the side effects of BRAF inhibitors and increase the period of effectiveness, doctors usually combine them with drugs named MEK inhibitors, trametinib, binimetinib, selumetinib, or cobimetinib. 

Triple therapy: Defines the therapy where a combination of BRAF and MEK inhibitors are brought together with immunotherapy drugs called checkpoint inhibitors (PD-1 and PD-L1 inhibitors). The aim of immunotherapy is to boost the immune system to fight cancer. 

Sources: 

hopkinsmedicine.org 

cancer.gov 

ncbi.nlm.nih.gov 

verywellhealth.com 

Biomarker Clinical Trials 

In 1998, the National Institutes of Health’s Working Group on Biomarker Definitions defined a biomarker as “a property that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention.” This means that the biomarkers represent a variety of parameters, including genomic features. The diagnosis itself, the histology of the tumor, and the age and sex of the patient count as biomarkers. Genomic markers are directly targeted by certain therapies and may affect their effectiveness.  

The International Cancer Genome Consortium is responsible for researching and publishing comprehensive genomic abnormalities (somatic mutations, abnormal gene expression, epigenetic modifications) in tumors from 50 different cancer types and/or subtypes.  

Biomarkers play an important role in illuminating the relationships between environmental exposures, human biology, and disease. Scientists can use biomarkers to better understand fundamental biological processes, measure the impact of environmental factors on health, and translate research findings into practical medical and public health applications.  

  

What Is A Biomarker Clinical Trial?  

A biomarker (short for biological marker) is an objective measure that captures what is going on in a particular cell or organism. They are often called tumor markers in cancer and are used to learn more about the tumors that are forming in the patient and to predict which treatment will work best. In clinical trials, biomarkers serve many practical uses, such as screening patients for relevance, subgrouping, and monitoring responses.  

Biomarkers can be defined as a kind of early warning system. For example, high levels of lead in the bloodstream may indicate the need for testing for the nervous system and cognitive disorders, especially in children. High cholesterol levels are a common biomarker for heart disease risk.  

Many biomarkers can be revealed by simple measurements made during a routine exam. Some biomarkers can be analyzed as a result of samples taken from whole blood, serum, plasma, circulation, or secretions such as feces, urine, nipple discharge, and saliva. Some biomarkers capture changes at the molecular and cellular levels by looking at genes or proteins.  

Biomarkers are measurable medical signs that enable reproducible measurements in the modern laboratory setting. The high mortality rates in cancer diseases are due to the lack of sufficient biomarkers to provide early diagnosis and, accordingly, the inability to develop targeted therapies. Rapid and reliable analysis of molecules in the laboratory environment enables new treatments in clinical trials. Including accompanying biomarkers in clinical research studies in all new drug trials for targeted therapies in the oncology field has become mandatory. For this reason, the use of biomarkers, especially those measured in the laboratory, in clinical research has become widespread recently.  

Ideal markers require minimally invasive sampling, are reliable, inexpensive, and highly sensitive and specific. Re-biopsy is often recommended in advanced settings, as clonal evolution can lead to differences in molecular characteristics between the original tumor and its metastases and even between metastatic lesions in a given patient. Among other uses, biomarkers may alert researchers to the need for early study termination (for example, if the biological effect is below the maximum tolerated dose).  

  

AKT1 Clinical Trials  

The AKT1 gene provides instructions for making a protein found in various cell types in the body called AKT1 kinase. Signals involving the AKT1 kinase are essential for the normal development and function of the nervous system. AKT1 kinase is involved in cell-to-cell communication between nerve cells (neurons), survival of neurons, and formation of memories. The AKT1 gene belongs to a class of genes known as oncogenes; when mutated, they cause normal cells to become cancerous. Glu17Lys mutation in the AKT1 gene is seen in proteus syndrome (overgrowth of connective tissue such as bones, ligaments, tendons, adipose tissue, skin, central nervous system, and various tissues in internal organs), schizophrenia (a brain disorder classified as psychosis, meaning it affects a person’s thinking, sense of self, and perceptions), breast, ovarian and colorectal cancers. In these cases, the mutation is somatic, meaning it is acquired during a person’s lifetime and is found only in tumor cells. The mutation aberrantly activates the AKT1 kinase, allowing cells to grow and divide without control or order. This unregulated cell proliferation leads to the development of cancerous tumors. There are 12 clinical trials with the AKT1 gene, completed and ongoing, in the U.S. National Library of Medicine.  

 

PIK3CA Clinical Trials  

The PIK3CA gene holds the instructions for making a protein called p110α. This protein is vital for many cell functions, including telling your cells when to grow and divide. Certain people may have mutations in this gene. PIK3CA gene mutations cause cells to grow uncontrollably, which can lead to cancer. PIK3CA gene mutations are linked to breast cancer and cancers of the ovary, lung, stomach, and brain. Breast cancer likely stems from changes to PIK3CA and other genes. PIK3CA mutations affect about 20 to 30 percent of all breast cancers and 40 percent of people with estrogen receptor (E.R.)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancers. ER-positive means your breast cancer grows in response to the hormone estrogen. HER2-negative means you don’t have abnormal HER2 proteins on the surface of your breast cancer cells. There are 106 clinical studies on the PIK3CA gene, completed and ongoing, in the U.S. National Library of Medicine.  

 

JAK2 Clinical Trials   

Mutations in JAK2 cause some bone marrow diseases. These are known as myeloproliferative neoplasms (MPNs), in which the bone marrow overproduces white blood cells, red blood cells, and/or platelets.   

Some of the MPNs most commonly associated with JAK2 are:   

Polycythaemia vera (P.V.), where the bone marrow makes too many red blood cells. Essential thrombocythaemia (E.T.), where there are too many platelet-producing cells (megakaryocytes) in the bone marrow. Primary myelofibrosis (PMF) is also known as chronic idiopathic myelofibrosis or agnogenic myeloid metaplasia. There are too many platelet-producing cells and cells that cause scar tissue in the bone marrow.  

There are 59 clinical studies on the JAK2 gene, completed and ongoing, in the U.S. National Library of Medicine.   

 

MET Clinical Trials  

The MET protein is produced by the MET gene. Contributes to cell development and signaling. The MET gene in cancer cells can change and create more MET proteins. This, in turn, can grow cancer cells, and the cells can spread throughout the body. It can be found in lung, liver, kidney, head, and neck cancers. MET gene amplification may enable cancerous cells to proliferate and spread more aggressively in some lung cancer cases, particularly non-small cell lung cancer, than in lung cancer cases without known biomarkers. Patients with MET amplification may respond better to MET-focused therapy than to typical therapies. There are 535 clinical studies on the MET gene, completed and ongoing, in the U.S. National Library of Medicine.  

  

NRG1 Clinical Trials   

NRG1 Fusions are genetic abnormalities found in a small percentage of patients with solid tumors. In these patients, too much of the growth factor NRG1 (sometimes called heregulin) can be produced, which can cause cancer cells to grow and divide uncontrollably. Oncogenic gene fusions are hybrid genes that result from structural DNA rearrangements and lead to dysregulated activity. Fusions containing the neuregulin-1 gene (NRG1) offer a rational candidate for targeted therapy. The most commonly reported NRG1 fusion is CD74-NRG1, which occurs most commonly in patients with invasive mucinous adenocarcinomas (IMAs) of the lung, although several other NRG1 fusion partners have been identified in patients with lung cancer, including ATP1B1, SDC4, and RBPMS. Clinical trials are ongoing for cancer patients with solid tumors with a specific genetic abnormality called NRG1 Fusion. There are 28 clinical studies on the NRG1 gene, completed and ongoing, in the U.S. National Library of Medicine.  

  

HER2 Clinical Trials  

HER2/neu is a protein involved in normal cell growth that may be larger than normal amounts by some types of cancer cells, including breast, ovarian, bladder, pancreatic, and stomach cancers. This may cause cancer cells to grow more quickly and spread to other parts of the body. Checking the amount of HER2/neu on some types of cancer cells may help plan treatment. Also called c-erbB-2, HER2, human EGF receptor 2, and human epidermal growth factor receptor 2. Because HER2 is associated with so many types of cancer, there is a significant amount of clinical research done on HER2. Cancer cells are likely to respond to treatment with drugs targeting the HER2 protein. The number of completed and ongoing clinical studies on the HER2 gene in the U.S. National Library of Medicine is 2461.  

  

ROS1 Clinical Trials  

A ROS1-positive lung cancer, also known as a ROS1 rearrangement in lung cancer, refers to any lung cancer that tests positive for a fusion in the ROS1 gene. ROS1 rearrangements occur in approximately 1-2 percent of patients with non-small cell lung cancer (NSCLC). ROS1-positive lung cancer tends to be aggressive and can spread to the brain and the bones. ROS1-positive lung cancer occurs when a gene called ROS1 fuses with a nearby gene. It has a critical role in the development and progression of many types of cancer, including lung cancer. Patients with a ROS1 rearrangement respond well to some of the same treatments that are used to treat ALK-positive lung cancer patients. Treatment of the ROS1 gene requires long-term drug use. It aims to minimize the activation of the kinase protein produced by the gene. The applied methods aim to minimize the activation of the ROS1 gene and the kinase protein produced by the gene. There are 89 clinical studies on the ROS1 gene, completed and ongoing, in the U.S. National Library of Medicine.  

 

ALK Clinical Trials   

Anaplastic lymphoma kinase (ALK) is a gene that helps in the development of the gut and nervous system. The ALK gene is present when you are only an embryo but gets turned off while still in the womb. The ALK gene codes for the anaplastic lymphoma kinase protein. It belongs to a family of proteins called receptor tyrosine kinases that are responsible for regulating cell growth. When a change or mutation occurs, the growth of the cell is no longer regulated properly, and abnormal cells are produced at an increased rate. ALK fusion clinical trials commonly treat solid malignant tumors, which are cancerous and do not contain cysts or liquid areas. Examples of solid tumors include sarcomas, carcinomas, and lymphomas. ALK fusion clinical trials are currently studying ALK inhibitor drug therapies. An ALK inhibiting drug inhibits proteins involved in the abnormal growth of tumor cells, which is why these drugs are more effective for patients with this gene alteration. There are 376 clinical trials on the ALK gene, completed and ongoing, in the U.S. National Library of Medicine. 

Sources: 

Ncbi.nlm.nih.gov 

Memoinoncology.com 

Niehs.nih.gov 

Frontiersin.org 

Medlineplus.gov 

Healthline.com 

Nrg1com.wpengine.com 

Cancer.gov 

Lcfamerica.org