What Is ALK-Positive Lung Cancer? 5 Facts To Know | MyLungCancerTeam

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What Is ALK-Positive Lung Cancer? 5 Facts To Know

Medically reviewed by Leonora Valdez, M.D.
Written by Aminah Wali, Ph.D.
Posted on April 19, 2024

For some people with lung cancer, mutations (changes) in their DNA can be the main cause of the disease. Doctors usually look at small pieces of tumor tissue under a microscope to learn more about a person’s lung cancer. They may also look for changes in the tumor DNA, called molecular markers or biomarkers.

Several different biomarkers can be found in lung cancer. One of them is an abnormal version of a protein called anaplastic lymphoma kinase (ALK). If your doctor finds a problem with the ALK protein in your lung tumor cells, then you have ALK-positive lung cancer.

ALK-positive lung cancer is a unique type of lung cancer in several different ways. This article covers important things you should know about ALK-positive lung cancer. Your doctor can help you better understand this diagnosis and how it may affect your treatment options and overall prognosis or outlook.

1. High Levels of ALK Protein Can Lead to Cancer

ALK is a protein that is important for cell growth. Normally, high levels of ALK protein are only present in developing embryos. Levels of ALK protein are usually very low in adults. However, mutations in the ALK gene can cause it to be “turned on” later in life and produce abnormally high levels of the ALK protein. If there’s too much ALK protein, cells can divide at the wrong time and cause cancer.

Different types of changes in the ALK gene can lead to high levels of the ALK protein, and the most common type of mutation in lung cancer is a gene rearrangement. This happens when parts of the DNA break off and reattach in the wrong spot, causing two different genes to fuse together.

While the ALK gene can fuse with many different genes, in lung cancer it usually joins together with a gene called EML4. This creates a new gene called EML4-ALK. If your lung cancer cells test positive for EML4-ALK, your doctor will say you have an “ALK fusion” or “ALK mutation.”

2. ALK-Positive Lung Cancer Is Usually Non-Small Cell Lung Cancer

Lung cancer can be divided into two main types — non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). ALK-positive lung cancer is generally NSCLC, which makes up the majority of all lung cancer cases.

About 5 percent of NSCLC cases are ALK-positive. Unlike with some other types of lung cancer, avoiding cigarettes doesn’t necessarily decrease your chances of developing ALK-positive lung cancer. Most cases of this cancer occur in people who smoke lightly or not at all.

Researchers have found that ALK-positive lung cancer is more common among certain racial and ethnic groups, specifically white Americans and Asian Americans. People with ALK fusions are also more likely to be diagnosed with lung cancer at a younger age compared to people with other types of lung cancer.

3. ALK-Positive Lung Cancer Is Diagnosed With Biomarker Testing

To see if your tumor cells contain an ALK fusion or another mutation commonly found in lung cancer, your doctor will suggest biomarker testing. This will usually require a biopsy (removing a piece of the tumor) so it can be studied in the lab.

Once the tumor cells have been collected, the technique that is most commonly used to test for the ALK fusion is called fluorescence in situ hybridization (FISH). FISH uses tiny molecules called probes that can recognize EML4 and ALK in cells. Each probe glows a different color to show where EML4 and ALK are. A doctor will add the probes to a tumor biopsy, and if the two colors appear right next to each other, that means the tumor is positive for EML4-ALK.

Immunohistochemistry (IHC) is another technique used to diagnose ALK-positive lung cancer. This technique uses antibodies, which are proteins that can recognize specific molecules on the surface of cells. To perform IHC, a doctor uses antibodies that specifically recognize EML4 and ALK to see if a tumor sample has an ALK fusion.

A doctor may use next-generation sequencing (NGS) to see whether tumor cells have ALK fusions. NGS can look at all the DNA in a sample and find mutations in any gene. Unlike FISH and IHC, which look specifically for EML4-ALK or other known ALK fusions, NGS can find other mutations in a tumor. This allows for more comprehensive biomarker testing.

4. ALK-Positive Lung Cancer Is Treated With Specific Therapies

Most people with NSCLC don’t get tested for ALK fusions until their cancer is at a more advanced stage. Therefore, surgery — which is often used to treat early-stage disease — is not typically used for ALK-positive lung cancer. Radiation therapy, on the other hand, may be used to treat some cases of advanced ALK-positive lung cancer if the tumor cells haven’t spread far throughout different parts of the body.

Most people with ALK-positive lung cancer will be treated first with an ALK tyrosine kinase inhibitor (TKI), also called an ALK inhibitor. This type of targeted therapy drug can specifically recognize the ALK protein. Generally, ALK inhibitors are the most effective treatments for ALK-positive lung cancer.

ALK inhibitors include:

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

While crizotinib may be prescribed first in some cases, many people will find that their cancer will eventually stop responding to the drug. If this happens to you, your doctor may try another ALK inhibitor, such as ceritinib or alectinib. Additionally, the cancer may metastasize (spread) to the brain or other parts of the central nervous system in some people. Alectinib or ceritinib may do a better job of treating ALK-positive lung cancer with brain metastases compared to crizotinib.

Doctors may also use chemotherapy to treat ALK-positive lung cancer, although it’s usually not the first treatment choice. Chemotherapy drugs can specifically kill cells that divide very quickly, like cancer cells. Compared to other types of lung cancer, ALK-positive lung cancer cells are especially sensitive to the chemotherapy drug pemetrexed (Alimta).

Read more about specific medications in this list of treatments for lung cancer.

5. ALK-Positive Lung Cancer May Stop Responding to Treatment

Although most people with ALK-positive lung cancer already have advanced disease at diagnosis, the overall prognosis (outlook) for the disease might be better compared to that of other types of advanced lung cancer.

One study found that around half of people who’d been treated for ALK-positive lung cancer lived for nearly seven years after diagnosis. This is longer than the median survival rate for other people with advanced NSCLC, which may be one to two years after diagnosis.

Although the prognosis for ALK-positive lung cancer may be better overall compared to other types of lung cancer, more effective treatment options are still needed. Because ALK-positive lung cancer often stops responding to treatment, clinical trials are needed to find newer treatments that can keep the cancer from getting worse.

If you have any questions about the most current therapies being tested for ALK-positive lung cancer, ask your doctor. They’ll be able to recommend the treatment options that may give you the best chance at better health and a longer life.

Talk With Others Who Understand

MyLungCancerTeam is the social support network for people with lung cancer and their loved ones. On MyLungCancerTeam, more than 12,000 members come together to ask questions, give advice, and share their stories with others who understand.

Do you have more questions about ALK-positive lung cancer? Have you or a loved one been diagnosed with ALK-positive lung cancer? Share your insights in the comments below, or start a conversation by posting on your Activities page.

    Posted on April 19, 2024
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    Leonora Valdez, M.D. received her medical degree from the Autonomous University of Guadalajara before pursuing a fellowship in internal medicine and subsequently in medical oncology at the National Cancer Institute. Learn more about her here.
    Aminah Wali, Ph.D. received her doctorate in genetics and molecular biology from the University of North Carolina at Chapel Hill. Learn more about her here.

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