Frequently asked questions

Frequently asked questions by the NTRK community on diagnosis, treatment, testing and disease management.

General Questions About NTRK fusion-positive cancer:

  • 1. What is NTRK gene fusion cancer?

      Cancer occurs when normal cells undergo a change that causes them to grow out of control. These changes occur in one or more genes inside the cell. NTRK gene fusion cancer is driven by changes in genes called NTRK (neurotrophic tyrosine receptor kinase).

      Normally, NTRK genes (1,2 and 3) are responsible for TRK proteins, involved in the healthy development and function of the nervous system. In the case of NTRK gene fusion cancer, part of the normal NTRK gene splits and binds with another normal gene, creating a ‘NTRK fusion oncogene’. NTRK fusion oncogenes produce abnormal ‘TRK fusion’ proteins, which help rewire normal cells into cancer cells and drive cancer growth. Cancer drivers like this can only be detected by biomarker ‘genomic’ testing.

  • 2. How frequent is NTRK gene fusion cancer and who is affected?

      NTRK gene fusions are found infrequently in common tumor types but are found frequently in certain rare tumors. (Knowledge about the frequency of NTRK gene fusions is based on small studies so we’ll find out more as NTRK testing continues)

      • In colorectal, breast, melanoma and lung cancer, NTRK gene fusions occur in 1-5% of cases. (In colorectal cancer, NTRK gene fusions may be more likely in tumors that are MSI-H.)
      • They are found in slightly higher frequency (up to 10% of cases) in certain gastro-intestinal stromal tumors (GIST), spitzoid melanoma, and thyroid cancers. The chance of finding a NTRK gene fusion is higher in children with thyroid cancer, increasing to 26% of cases.

      Rare and unusual tumor types in which NTRK gene fusions are commonly detected include:

      • Infantile Fibrosarcoma: An extremely rare childhood tumor, where NTRK gene fusions appear to be detected in 70% to 91% of cases
      • Secretory Breast and Salivary Gland Carcinomas: These may harbor NTRK gene fusions in up to 90% of cases
      • Congenital Mesoblastic Nephroma: A rare kidney tumor, most likely to be found in newborns and young children. Not all cases are cancerous and the chance of NTRK gene fusions vary
      • Brain Tumors: NTRK gene fusions may be more likely in high-grade gliomas, particularly in younger patients
  • 3. What is a genomic alteration or cancer driver gene?

      Genomic alterations are abnormal changes to the genetic code of a cell. Such changes happen routinely in the human body, but most of the time the body is able to fix the mistake or cause the damaged cell to self-destruct. Sometimes, the cell is able to survive and because of the change to its genetic code, starts growing out of control and replicating faulty copies.

      With advances in cancer research, it became possible to look at the genetic information of cancer cells and, in some cases, determine which genetic alterations are causing the cancer. Researchers started developing new treatments to specifically target these alterations.

      There are different genomic targets, including: ROS1 fusion, NTRK gene fusions, EGFR mutations, ALK translocation, BRAF mutation, BRCA1 and BRCA2 mutations and HER-2/neu overexpression, c-KIT mutations etc. These alterations drive tumor growth and are often referred to as cancer driver genes.

  • 4. What is the difference between gene fusions and mutations?

      Both gene fusions and mutations are errors in the genetic code. In cancer, these errors cause the cells to grow out of control.  A mutation is like a mis-spelled word; one or more incorrect letters have been used. A fusion is like two words that get stuck together without a space or that actually have their letters intermingled—they are “fused” together.

  • 5. Can you be born with NTRK gene fusion cancer?

      NTRK gene fusions do not appear to be hereditary, i.e. they cannot be passed on from your parents or to your offspring.

      In very rare cases, babies are born with tumors, which may be cancerous. In such an unusual case, Doctors may decide to test the tumor for genomic alterations, including NTRK. If the test is positive for NTRK gene fusions, it is not because the baby inherited the fusion but rather because something went wrong in a single cell while the baby was developing in the womb.

  • 6. How do you test for NTRK gene fusions in cancer? What is required?

      A newly or previously collected small tissue sample or circulating blood (cfDNA) is tested. The sample is sent to a certified laboratory where the DNA of the cancer cells is extracted and scanned for abnormalities. The abnormalities are compared with known alterations that can drive cancer. The information is shared with your Medical team.

  • 7. Should I be tested for NTRK gene fusions?

      NTRK testing is not routine. Speak with your Doctor about testing for genomic alterations, including NTRK gene fusions. This type of testing may depend on your tumor type, characteristics of your tumor, whether your cancer is responding to standard therapy, and the results of previous tests.

  • 8. What does a positive NTRK gene fusion result mean for treatment? What are my options?

      If doctors find a specific cancer driver like a NTRK gene fusion and you are not responding to standard therapy, they may consider a treatment tailored to your individual cancer type – this is called precision medicine. Some precision medicines may be approved for use already or be in clinical trials for further research.  For more information on a list of NTRK studies, you can check the links below.

      Clinical (Global)

      EU clinical trials register (EU)

      Cancer Support Community Clinical Trials Matching Service (US)

Questions About Biomarker ‘Genomic’ Testing (sometimes known as molecular profiling)

  • 1. What is a biomarker?

      In medicine, biomarkers are any measurable substance that can provide information relevant to the health of the person being tested. Biomarkers may be present in a tumor, or even in blood or other bodily fluids. Some biomarkers predict a person’s likelihood to develop a disease. Others show if a person already has a disease, or how severe the disease is. Increasingly, doctors are using biomarkers to determine if a patient is likely to respond to a specific treatment.

      In cancer, these biomarkers most often test for specific cancer-associated genomic alterations (i.e. abnormal changes to the genetic code of a cell) and abnormal protein expressions that may be suitable for a specific treatment.

      All cancer cells have mutations or genomic alterations. (In fact, mutations and genomic alterations occur in normal cells as well.) Most of those changes are not harmful and do not impact the cell or the body. When doing biomarker testing, doctors are looking only for those changes that are harmful, that are causing the cancer cells to grow out of control.

  • 2. What can biomarker (genomic tests) find and who is it for?

      Biomarker testing can include genomic tests that look for specific genetic changes or alterations in cancer cells that could be driving tumor growth. The hope is to find information that can help identify a specific ‘personalised’ treatment.

      There are many different genomic targets, including: ROS1 fusion, NTRK gene fusions, EGFR mutations, ALK translocation, BRAF mutation, BRCA1 and BRCA2 mutations and HER-2/neu overexpression, c-KIT mutations etc.

      Genomic testing is not routinely undertaken for all cancer cases and does not always find a target that is helpful for treatment. It is best to discuss options with your Doctor and medical team.

  • 3. How is genomic testing different from genetic testing in oncology?

      Genomic testing looks for alterations, mutations or pathways in cancer cells, which could be driving the cancer

      Genetic testing: Looks at the genes to see if a hereditary cancer syndrome is present.

  • 4. What should I ask my Doctor about testing?

      You may want to ask the following questions:

      • Have I had biomarker testing already?
        • If so, for what biomarkers was I tested? Did this include genomic alterations like NTRK?
        • What did the tests reveal?
      • If no, what could further tests find?
      • How could genomic testing results be helpful?
      • What type of genomic test would you recommend?
  • 5. How is the test conducted and what is involved for me?

      Some tests can be done using a blood sample (cfDNA), but most tests require a piece of your tumor. If you are having surgery, or have recently had surgery, the test can be done on some of the tumor that was removed at the time. Because tumors can change over time, sometimes doctors will request a new tumor sample. This usually is much less invasive than the original surgery, as only a small piece of tissue is required.

      The sample is sent to a certified laboratory where the DNA and sometimes RNA of the cancer cells is extracted and scanned for abnormalities. The abnormalities are compared with known alterations and the information shared with your Medical team. There is a wait for results. Depending on the kind of tests ordered and the specific laboratory, this wait can be two or three days or as long as three or four weeks. During this time, you may or may not be receiving treatment. While the delay can be frustrating, your doctor will take this into consideration when planning treatment.

  • 6. Are there different types of tests for NTRK gene fusions? What are the differences?

      There are several tests to detect genomic alterations like NTRK gene fusions. These include:

      (Adapted from Colorectal Cancer Alliance)

      • Immunohistochemistry (IHC) detects NTRK (fusion) proteins in a tumor sample
      • Fluorescence In situ Hybridization (FISH) detects gene changes (rearrangements or gene copy number changes) in a cell, but cannot indicate if an abnormal protein is being made by that mutation; these proteins are oncogenic (i.e. ‘drivers’ of cancer cells)
      • RT-PCR (Reverse-Transcriptase-Polymerase Chain Reaction) amplifies the DNA at the point where the NTRK gene has fused with a partner gene. This method works only when NTRK is fused to a known partner gene
      • Next generation Sequencing (NGS) looks at sequences in DNA or RNA and so can test for many different gene defects at once. NGS is also known as comprehensive biomarker testing.
  • 7. When is the best time to test for NTRK gene fusions?

      Talk to your doctor about when testing should be done. In some cases, testing can take place early in the diagnosis, particularly if surgery or biopsy is already required. In other cases, the doctor may suggest waiting until after trying treatments that do not require a biomarker.

      You should discuss tumor tests with your Doctor, particularly if your cancer cannot be treated with standard therapy. Testing for NTRK is likely to be done in tumors with a high chance of NTRK gene fusions. In common tumors, where NTRK alterations are rare, doctors may rule out more usual markers first before testing for NTRK unless using NGS (comprehensive biomarker) testing.

  • 8. Who carries out the test?

      The biopsy (tumor sample) or the blood test (cfDNA) will be taken by your Medical team and sent to a certified laboratory for testing. A pathologist or a molecular biologist performs the test and interprets results to share with your hospital team.

  • 9. How long will it take to get the results?

      There is a wait for results. Depending on the kind of tests ordered and the specific laboratory, this wait can be two or three days or as long as three or four weeks. During this time, you may or may not be receiving treatment.

  • 10. How do I understand my results and what they mean for treatment?

      Talk with your doctor about your test results. Generally, but not always, a positive result means that you may be eligible to be treated with a biomarker-driven therapy at some point. Depending on your specific case, however, your doctor may prefer to use other traditional therapies first and save the biomarker-driven therapy for use later, if needed.

  • 11. Does the test need to be repeated if my cancer progresses?

      This depends on several factors, including if doctors have enough tumor tissue to test. Depending on how much time has lapsed, some doctors prefer to conduct a second test on a fresh biopsy. This is because tumors can acquire new genetic alterations over time. Generally, if a NTRK-fusion cancer gets worse while on a TRK Inhibitor, there should be a second test to see if cancer cells have developed other mutations that can explain resistance.

  • 12. What happens if my Doctor recommends NTRK gene fusion testing but my insurance company or healthcare authority won’t pay?

      There may be options. One option is to work with your doctor’s office; sometimes the review board will change their mind and pay for the test. There are also financial support programs offered from both non-profit companies and brand-specific organizations. See our “Useful Links” section for more details.