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 fuses, or joins, with a piece of another, unrelated gene. This fusion activates the NTRK gene in a way that causes uncontrolled cell growth and cancer. NTRK gene fusions can occur in many different types of cancer, but they are rare in lung cancer, found in less than 1% of all lung cancer cases. Even though they are uncommon, it is very important to know if you have one, because there is an effective treatment available for patients whose lung cancer has NTRK gene fusions.

Who is most likely to have an NTRK gene fusion?

Currently, research has not shown any specific patient group of demographic that is most, or more, likely to have an NTRK gene fusion. This means that anyone with lung cancer could have these fusions, so testing is recommended for all patients. 

What are the types of NTRK gene fusions?

There are three different types of NTRK genes: NTRK 1, NTRK 2 and NTRK 3. These gene fusions are named after the two genes that have joined together. If you have an NTRK gene fusion, your report may list it as “NTRK” followed by the name of the gene it fused with. Treatment is generally the same regardless of which type of NTRK gene fusion you have.

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

There are several different tests that can detect NTRK gene fusions, including next-generation sequencing (NGS). NGS testing 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 check for NTRK gene fusions, so it is best to talk to your doctor to make sure that you are getting the most comprehensive test available.

In some situations, a patient may not be able to have the biopsy needed to perform NGS testing, 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 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 work by directly targeting, or inhibiting, the gene 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. 

It is important to know that NTRK gene fusions are different than NTRK mutations. A fusion is when two genes join, and a mutation is a change in the gene sequence. Think of DNA like words in a book, a fusion is two words stuck together, while a mutation is words out of order.

Both fusions and mutations can cause uncontrolled cell growth which can lead to cancer, but currently, only NTRK gene fusions have treatments available. Treatment for NTRK mutations is still being studied in clinical trials. Researchers are also examining if patients who have an NTRK gene fusion who later 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.