What Is ROS1-Positive Lung Cancer?

ROS1-positive lung cancer refers to cases of lung cancer in which the patient is positive for a mutation of the ROS1 gene. The ROS1 gene is responsible for making the protein ROS1, which signals cells to grow and reproduce. If a lung cancer patient is ROS1-positive, the cancer is usually more aggressive due to the ROS1 protein causing more abnormal cells to drive the growth of the tumor. However, ROS1-positive patients may be eligible for checkpoint inhibitors for treatment, which block the mutation from causing the cancerous cells to rapidly grow and divide.

What Is the ROS1 Mutation?

ROS1 is classified as an oncogene. This means in the normal operation of the body, it is involved in cell growth, but in the event of a mutation, it becomes cancerous. The ROS1 mutation related to non-small cell lung cancer (NSCLC) occurs in form of a fusion, meaning that the ROS1 gene links or unites with another gene, changing its usual instructions sent to the cells, causing their non-stop growth, thus cancer. This continuous instruction sent to the cells drives the growth of cancer, thus this type of change in genes is called driver mutation.

Although rare, the identification of the ROS1 fusion can play a major role in the patient’s treatment plan. Other than lung cancer, the ROS1 mutation has been identified in the following cancer types:

Glioblastoma multiforme
Bile duct cancer
Ovarian cancer
Colorectal cancer

How Do You Know If You Have ROS1-Positive Non-small Cell Lung Cancer?

ROS1-positive lung cancer has only been identified in non-small cell lung cancer (NSCLC), and not in small cell lung cancer. Of all NSCLC cases, about 2 percent of them are ROS1 positive. This has led to an increase in testing for NSCLC patients.

To be eligible for targeted therapies, cancer patients need a positive test for the ROS1 mutation. Typically, a tissue sample of the tumor is collected by the doctor, and it is sent to a laboratory for results. The tests used for the ROS1 mutation include:

Fluorescence in situ hybridization (FISH): The most common testing method used locates specific DNA sequences by exposing chromosomes to a probe with a fluorescent molecule attached. A researcher will be able to identify if the ROS1 gene if the fluorescent probe has been bound to it.
Multiplex real-time PCR assays: Test that covers a range of fusion genes. Inexpensive and quick results compared to other tests. This test uses multiple probes that can be distinguished from the rest of the DNA sequences.
Immunohistochemistry: Uses antibodies against the ROS1 protein to detect any abnormalities. This test is for screening to diagnose cancers, so it can be used initially to avoid unnecessary FISH tests.
Next-Generation Sequencing (NGS): Looks at the entire human genome in one test to detect any mutation. NGS is the most comprehensive test available but may be expensive and time-consuming compared to other testing methods.

What Are the Risk Groups for ROS1-Positive Non-small Cell Lung Cancer?

Some mutations are inherited, passed from the parents at birth, and some are not. The ROS1 mutation is not classified as an inherited type of mutation, meaning they are acquired as the patient lives on. Other than genetic factors, there are various factors considered to identify if a patient is in the risk group or not.

Sex: Lung cancer in broader terms is seen more frequently in male patients, but about 65 percent of ROS1-positive NSCLC patients are females.
Age: The median age for lung cancer is 72, whereas it is estimated to be around 50 in ROS1-positive NSCLC patients.
Smoking: Although the Center for Disease Control and Prevention says smoking is the number one risk factor for lung cancer, it is hard to say the same for NSCLC. About 68 percent of the patients diagnosed with ROS1-positive NSCLC have never smoked in their lives.

ROS1-Positive Non-small Cell Lung Cancer Prognosis

ROS1-positive NSCLC is an aggressive type of cancer, meaning it grows and spreads rapidly. That is why it is generally diagnosed in advanced stages, where targeted therapy and immunotherapy are productive options for treatment.

The 5-year survival rate for NSCLC is 26 percent. The type and stage affect the prognosis.

Localized NSCLC: When the disease is localized (not spread to other parts of the body), the overall 5-year survival rate is 63 percent.
Regional NSCLC: If the cancer spreads to the nearby lymph nodes but not to other parts of the body, the 5-year survival rate drops to 35 percent.
Metastatic NSCLC: When the cancer spreads to other parts of the body, the 5-year survival rate decreases to 7 percent.

The targeted therapy drugs for ROS1-positive NSCLC do not aim to cure cancer but to stop the spread and manage it while providing the patient a longer and more enjoyable life.

What Are the Treatment Options for Someone with ROS1-Positive Cancer?

Targeted therapy is an encouraged treatment option for ROS1-positive NSCLC patients, and there are currently two ROS1 inhibitors approved by the FDA: Crizotinib (Xalkori), Entrectinib (Rozlytrek). These drugs, called ROS1 inhibitors, are in form of pills and taken orally. In targeted therapy, the treatment is achieved by attacking only the cancerous cells, rather than the whole body as in chemotherapy. Although it might present side effects (such as dizziness, diarrhea, constipation, fatigue and changes in vision), it generally causes less harm to the patient as the immune system is less damaged.

ROS1-Positive Non-small Cell Lung Clinical Trials

All the treatments available today helping patients overcome cancer are the result of thorough clinical trials. There are many clinical trials available for patients in different stages of NSCLC, aiming to evaluate innovative methods for patients whether they have localized or metastatic cancer, have abnormal genes, had prior treatment, and if their disease is progressing or not. Talk to your doctor to see if you are eligible for any clinical trials.

Massive Bio can help you understand if you are eligible for targeted therapies, immunotherapy and other clinical studies. Regardless of your geographical location or past medical history, you can participate in a clinical trial that has been examined and decided by experts, tailored to your specific cancer type, biomarkers and needs.

Massive Bio uses SYNERGY Artificial Intelligence (AI) platform to help you match the most appropriate clinical research based on your cancer type and the current stage of the disease. With more than 170 special clinical algorithms on the platform, Massive Bio fills the gap between patients with clinical research, to help you find novel treatments in real-time. We are here to help you in your fight against cancer. Feel free to get a free consultation and explore your clinical trial options.

Info Summary – ROS1 Positive Lung Cancer Clinical Trials

The only FDA approved treatments for ROS1 positive lung cancer are Crizotinib (Xalkori) and entrectinib (Rozlytrek). These targeted therapies can locate the abnormalities within cells (mutations) to know which cells to attack. This helps treatment avoid damaging healthy cells to minimize side effects compared to standard treatments.

Common side effects of ROS1 inhibitors include:

-Dizziness

-Diarrhea

-Constipation

-Fatigue

-Changes in vision

There are also ongoing clinical trials evaluating new therapies for ROS1 cancers. There are both clinical trials specifically for the ROS1 mutation, and many others available to treat lung cancer. Talk with your doctor to see if clinical trials could benefit you. Other drugs available for ROS1 lung cancer cases include Lorlatinib and Ceritinib. These therapies are often taken by themselves or in combination with chemotherapy and other treatments.

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