What Is ALK (Anaplastic Lymphoma Kinase)?

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 you are still in the womb.

ALK was originally discovered in cases of lymphoma, but most tumors that are ALK-positive cancer are non-small cell lung cancer. The gene most often fused with ALK is EML4.

What Is an ALK fusion?

For some individuals, the signaling pathway for ALK gets turned back on and fuses (joins) with another gene. This gene change is called an ALK fusion or ALK rearrangement and can lead to the development of cancer. When ALK fuses with another gene and causes cancer, it is described as ALK-positive. When this mutation is present, cancer cells are overproduced and can spread to other parts of the body.

What Does Anaplastic Lymphoma Kinase (ALK) Do?

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 cell growth is no longer regulated properly and abnormal cells are produced at an increased rate.

What Is ALK-Positive Cancer?

ALK-positive cancer describes cancerous cells with the ALK protein on the surface or an alteration of the ALK gene. Cells with the altered ALK gene will grow too quickly, causing the cancer to spread throughout the body at a quicker rate. Cancers that are seen with ALK fusions and mutations include neuroblastoma, non-small cell lung cancer, and anaplastic large cell lymphoma (anaplastic lymphoma kinase positive).

Roughly 72,000 patients are diagnosed with ALK-positive lung cancer each year worldwide. This is the cancer type most commonly seen with ALK fusions and mutations, followed by lymphoma.

What Are the Symptoms of ALK-Positive Cancer?

Having ALK present does not typically change the symptoms patients experience. However, because of the increase in abnormal cells, it can worsen symptoms and cause them in less time from the cancer spreading at a faster rate.

Symptoms of ALK-positive cancer depend on the specific type of cancer you have. For example, the symptoms of ALK-positive ALCL are:

Swollen lymph nodes
Unexplained weight loss
Night sweats
Shortness of breath
Discomfort in the stomach or chest
Anemia

The symptoms of ALK-positive lung cancer include:

Persistent cough
Wheezing
Shortness of breath
Unexplained weight loss
Hoarse voice
Fatigue
Chest pain that worsens when you cough or laugh

Symptoms can vary based on the cancer type that has ALK present. Talk with your doctor about your symptoms if you have any concerns or are interested in testing for ALK and other biomarkers.

Diagnosis and Treatment of ALK-Positive Cancer

If a cancer patient wants gene testing to determine what biomarkers are present, a sample of the tumor tissue is taken through a biopsy procedure. If a surgical procedure has already been planned, the sample can be taken then. Once the sample is collected, a pathologist will view the tissue underneath a microscope and then test the sample for the presence of ALK.

Testing methods include:

FISH analysis: Genetic abnormalities in chromosomes are viewed under a microscope to detect cancer or predict the patient’s outcome.
Immunohistochemistry: A special staining process is performed on the cancer tissue to show if the ALK alteration is present. Proteins in the cell are viewed under a microscope to detect their presence.
Next generation sequencing (NGS): A machine looks at the entire genome sequence in the body at once to detect any biomarkers, which are biological molecules produced by the body or tumor in a person with cancer.
Liquid biopsy: A sample of blood is taken and the test searches for the presence of tumor DNA and biomarkers such as ALK.

Treatment options for ALK-positive cancer depends on several factors such as the patient’s age, specific cancer type, symptoms, and previous treatments. Patients with ALK-positive cancer will likely be treated with a tyrosine kinase inhibitor (TKI) or ALK-inhibitor.

Targeted therapies that are ALK inhibitors include:

Crizotinib (Xalkori)
Ceritinib (Zykadia)
Lorlatinib (Lorbrena)
Alectinib (Alecensa)
Brigatinib (Alunbrig)

In some ALK-positive cancers, targeted therapies often stop being as effective within 1-2 years. Doctors will then choose from the following treatment options based on the patient’s individual case:

A different ALK-inhibitor from the one previously used. Additional testing may determine if a specific ALK inhibitor would be more beneficial.
Increasing the dose of the current ALK-inhibitor used
Pemetrexed-based chemotherapy, which works well in ALK-positive lung cancers.
Radiation therapy to slow the spread of cancer cells
Clinical trials for ALK-positive cancer

ALK-Positive Anaplastic Large Cell Lymphoma

Anaplastic large cell lymphoma (ALCL) is a rare type of non-Hodgkin’s lymphoma, which develops in T- cells. The ALCL cells appear large, undeveloped, and abnormal (anaplastic). ALCL typically occurs in patients that are in their 30’s or younger and is usually seen in males three times as much as females.

Most cases of ALCL are ALK-positive, where the abnormal T-cells have a mutation causing the ALK proteins to be produced. This is one of the more aggressive types of non-Hodgkin’s lymphoma. Roughly 70 percent of ALCL patients are ALK-positive and may benefit from targeted therapies that kill ALK-positive cells.

ALK Fusion Clinical Trials

Massive Bio specializes in finding advanced clinical trial treatments for all ALK-positive cancers. If you’ve been diagnosed with any ALK-positive cancer. If you don’t know which type of mutation or biomarkers you have, that’s okay. You can request a free consultation from our experts. Additional testing can help you determine your exact diagnosis. Many clinical research studies are monitoring targeted therapies that are designed for specific cancer types. Massive Bio recommends NGS testing for patients to help determine an exact diagnosis.

Sources:

https://www.cancer.gov

https://lymphoma-action.org

https://www.healthline.com