What is NTRK gene fusion?
A NTRK gene fusion is a mutation that occurs at a piece of a
chromosome containing NTRK gene, causing break off and re-join of
it with a gene at another chromosome. NTRK gene fusion leads to
activation of downstream signalling pathways and acts as an
oncogenic-driver for multiple types of paediatric and adult solid
tumours. NTRK gene fusion can present across cancer including
breast cancer and non-small cell lung cancer.
NTRK gene can abnormally fuse with other genes resulting in
growth signals that lead to carcinoma at different organs in the human
body. Although TRK gene fusion pan-cancer is rare, it can be
present in any patient regardless of age (adult or paediatric).
Why is it important? Significance of NTRK gene fusion
NTRK gene fusions can be found in approximately 1% of solid
tumours and more than 20 tumour types. In certain rare tumour type, such
as secretory breast cancer and congenital meroblastic nephroma, these
fusions are considered as pathogenic and they can occur in more than 90%
Other tumours with lower NTRK fusion frequencies (5-25%) include
papillary thyroid cancer and pediatric gliomas etc. Nevertheless,
NTRK gene fusion is also detected in less than 5% of the wide
range of common tumours such as adult brain tumour, non-small cell lung
cancer, breast and renal cell carcinoma.
Biomarker for pan-cancer TRK inhibitors
For the past decades, oncology treatment has been approved for cancer
indication based on tumour histological findings at the primary cancer
site. With the recent approval of treatments for patients with
NTRK gene fusion, biomarker-guided companion diagnostic is
driving a paradigm shift of cancer treatment.
NTRK gene fusion was discovered as a pan-cancer biomarker, which
can be found in most tumour types. Patients with
NTRK fusion-positive cancers are associated with high response
rates to TRK inhibitor therapies (e.g. larotrectinib and entrectinib).
Therefore, NTRK fusion biomarker test can be useful in guiding
treatment for individuals was solid tumours.