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What are NTRK fusions?

The NTRK genes (1, 2 and 3) exist in each of the cells within our body and contain the information for making three highly similar proteins: TRK-A, TRK-B, and TRK-C. The normal (wild type) 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 divide1. It is highly uncommon, and scientists don’t fully know the reason why NTRK genes can randomly join with (also called “fused to”) other non-related genes. The NTRK-fused genes can sometimes produce new NTRK fusion proteins that did not exist previously in the cells. These new NTRK fusion proteins are super-active and promote endless cell growth and division.

What does NTRK fusions mean?

When and how should I have NTRK fusions biomarker testing?

Because NTRK fusions are very rare, not everyone diagnosed with stage IV, metastatic colorectal cancer (mCRC), will be tested immediately for this variation2,3. If your metastatic tumor has no mutations in the KRAS/NRAS/BRAF/HER2 genes, but it does not stop growing with chemotherapy, you should discuss options for NTRK fusions testing with your doctor. If you had biomarker testing through a multi-gene panel (using new generation sequencing or NGS), NTRK results should be included.

There are several ways to test for NTRK fusions. All testing should be done in CLIA-certified laboratories. It is highly recommended to confirm positive results in one test by using another technique.

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.

An NTRK fusion protein is a prognostic biomarker for aggressive cancer.

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 have microsatellite instability (MSI-H). Discuss other biomarkers with your doctor so you can decide together on the best treatment for your tumor.

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