What are NTRK fusions?
There are 3 NTRK genes (1, 2 and 3) that contain the information for making three similar proteins: TRK-A, TRK-B, and TRK-C. The normal TRK proteins are receptors mostly found on the surface of cells of the nervous system. Their role is to receive signals from neighboring neurons to instruct cells to grow and divide. It is rare but the NTRK genes can fuse with other non-related genes which then produce new NTRK fusion proteins that promote uncontrolled cell growth and division in cancer cells.
What does NTRK fusions mean?
When and how should I have NTRK fusions biomarker testing?
NTRK fusions are very rare in metastatic colorectal cancer and therefore routine testing is not recommended. The NTRK fusion is different from a mutation. The fusion will be reported if you have comprehensive biomarker testing by Next Generation Sequencing (NGS). Individual NTRK fusion testing should be limited to those that are wildtype (no mutations) in KRAS, BRAF, NRAS and MSI-H. This testing can be done using different methods.
There are several ways to test for NTRK fusions. All testing should be done in CLIA-certified laboratories. It is recommended that all positive results be confirmed using one of the other available methods.
What do I do with this information?
Knowing the details of tumor biomarkers can help you and your doctor make decisions about personalized treatment with therapies tailored specifically to the characteristics of your tumor.
What treatment options are available?
If you were diagnosed with metastatic colorectal cancer with an NTRK fusion, and your tumor continues to progress during standard therapies, you are eligible for treatment with one of two newly FDA-approved NTRK inhibitors: larotrectinib or entrectinib.
Research has shown that a high proportion of tumors with an NTRK fusion protein also are microsatellite instability (MSI-H).
What are the common side effects of NTRK-targeted therapies?
Every treatment has the potential to cause some side effects. Some people may be more sensitive than others to a drug. The response to a specific treatment also depends on your medications, vitamins, and herbal supplements.
Tell your doctor and pharmacist about all your medications, vitamins, and treatments. If you are experiencing severe side effects, call your doctor immediately.
NTRK inhibitors may affect the nervous system and cause confusion, difficulty speaking, dizziness, coordination problems, tingling, numbness, or burning sensations in your hands and feet. They may cause fatigue, diarrhea or constipation, liver problems, joint or muscle pain, and anemia/low red blood cell levels.
It is unlikely that you will have all these side effects, but you might experience some of them. Call your doctor immediately if you are experiencing severe symptoms.
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