NTRK fusions and colorectal cancer

NTRK fusions occur when a piece of the NTRK gene splits off and connects to an unrelated gene. The fusion of these two pieces can cause cancer growth.

NTRK fusions happen early in the development of cancer. The abnormal fusion of proteins is the driving force of tumor growth.

Less than one percent of colorectal cancer patients have an NTRK fusion protein in their tumor. It is not hereditary (not a germline mutation) and does not pass from one generation to another in a family.. It is a somatic (acquired) mutation that happens randomly. NTRK fusions occur only in tumor cells.

Because NTRK fusions are very rare, routine testing is not recommended.

NTRK fusion proteins are seen more commonly in microsatellite instability (MSI-H) tumors, so your doctor may want to test you for NTRK fusions if you have the MSI-H biomarker.

If you were diagnosed with metastatic colorectal cancer with an NTRK fusion, and your tumor continues to progress during standard therapies, you may benefit from treatment with one of two FDA-approved TRK inhibitors: larotrectinib or entrectinib.

These therapies work by targeting TRK fusion proteins and blocking its signals to stop or slow cancer cell growth.

Every treatment has the potential to cause some side effects. Some people may be more sensitive than others to a particular drug.

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 of these side effects, but you might have some of them. Contact your doctor immediately if you are experiencing severe symptom.