NTRK and Lung Cancer

What is an NTRK gene fusion?

Errors in the NTRK gene are one type of lung cancer biomarker. In a tumor with an NTRK gene fusion, a piece of the NTRK gene and a piece of an unrelated gene fuse, or join, together. This activates the NTRK gene in a way that causes uncontrolled cell growth and cancer. NTRK gene fusions are present in many different types of cancer but are rare in lung cancer, accounting for less than 1% of all lung cancer cases. However, there is an effective treatment for NTRK gene fusions in lung cancer, so it is very important to know if a patient has one.

Who is most likely to have an NTRK gene fusion?

There currently is no research showing that any one type of patient demographic is most, or more, likely to have an NTRK gene fusion.

What are the types of NTRK gene fusions?

There are three different types of NTRK genes called NTRK 1, 2 and 3. The fusions are named by the two genes that are fused together. If you have an NTRK gene fusion, you might see “NTRK” followed by the name of the gene it fused with listed on your reports. In general, treatment is the same no matter which type of NTRK gene fusion you have.

How do you know if you have an NTRK gene fusion?

Several different tests can detect NTRK gene fusions, including next-generation sequencing (NGS). NGS places tissue from a patient’s tumor that has been gathered from a biopsy into a machine that looks for many possible biomarkers at one time. Not all NGS tests include NTRK gene fusions, so it is best to talk to your doctor to make sure that you are getting the most comprehensive test available.

There may be some situations where a patient can’t undergo the biopsy needed to perform NGS, so a liquid biopsy may be recommended instead. A liquid biopsy can look for certain biomarkers in a patient’s blood. Talk to your doctor to make sure one of these tests was performed.

Learn more about the different types of biomarker tests.

What is the course of treatment like for someone with an NTRK gene fusion?

Knowing if you have an NTRK gene fusion is important no matter your stage of lung cancer. However, it has the most treatment implications for stage four patients.

Currently, the approved targeted therapies for NTRK gene fusions in lung cancer are entrectinib (Rozlytrek), larotrectinib (Vitraki) and Augtyro™ (repotrectinib). These drugs are given in pill form and directly target, or inhibit, the fusion that is making the cancer grow.

Other treatment options for patients with NTRK gene fusions may include clinical trials, chemotherapy or chemotherapy plus immunotherapy. 

One important thing to note is that NTRK gene fusions are different than NTRK mutations. A fusion is when two genes join, and a mutation is when there is a change in the gene sequence. If you think of DNA as words in a book, a fusion would be two words stuck together, whereas a mutation would be words out of order.

Both fusions and mutations can cause uncontrolled cell growth which can lead to cancer. There are treatments available for NTRK gene fusions, but not for NTRK mutations. However, treatment for NTRK mutations is being studied in clinical trials. Researchers are examining if patients who have an NTRK fusion and then develop an NTRK mutation are less likely to respond to the NTRK-inhibitor drugs. Talk with your doctor about participating in a clinical trial.

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

1. What is the goal of this treatment?
2. What are the potential side effects?
3. What other options do I have?

Research is happening at a rapid pace and your doctor should be up to date on the recommendations for your specific type of lung cancer. If you don’t feel comfortable with the answers you are receiving, do not hesitate to seek out a second opinion.