The neurotrophic tyrosine receptor kinase (NTRK) gene family encodes three tropomyosin receptor kinases (TRKA, TRKB, TRKC) that contribute to central and peripheral nervous system development and function. NTRK gene fusions are oncogenic drivers of various adult and paediatric tumours. Several methods have been used to detect NTRK gene fusions including immunohistochemistry, fluorescence in situ hybridisation, reverse transcriptase polymerase chain reaction, and DNA- or RNA-based next-generation sequencing. For patients with TRK fusion cancer, TRK inhibition is an important therapeutic target. Following the FDA approval of the selective TRK inhibitor, larotrectinib, as well as the ongoing development of multi-kinase inhibitors with activity in TRK fusion cancer, testing for NTRK gene fusions should become part of the standard diagnostic process. In this review we discuss the biology of NTRK gene fusions, and we present a testing algorithm to aid detection of these gene fusions in clinical practice and guide treatment decisions.
- ntrk gene fusions
- trk fusion cancer
- cancer screening
- tyrosine kinase inhibitor
- tumour-agnostic biomarker
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Handling editor Newton ACS Wong.
Contributors All authors contributed equally to the preparation, drafting and reviewing of the manuscript. Medical writing support, including assisting authors with the development of the outline and initial draft, incorporation of comments and preparation of tables and figures, was provided by Penny Butcher, PhD and Alison Scott, PhD; editorial support, including fact-checking, referencing, figure preparation, formatting, proofreading and submission was provided by Annabel Ola, MSc, all of Scion (London, UK), supported by Bayer Healthcare Pharmaceuticals and Loxo Oncology according to Good Publication Practice guidelines (http://annals.org/aim/article/2424869/good-publication-practice-communicating-company-sponsored-medical-research-gpp3).
Competing interests FP-L has participated in advisory boards for Bayer, Roche, Illumina and Nanostring, and been involved in studies sponsored by Bayer. ERR has had a role as an expert consultant, participated in a meeting and participated in an advisory board for Bayer Healthcare Pharmaceuticals. ARS has had a role as an expert consultant for Merck US, Bristol Meyers Squibb and Bayer Healthcare Pharmaceuticals; participated in meetings for Merck US, Bristol Meyers Squibb and Bayer Healthcare Pharmaceuticals; participated in advisory boards for Merck US, Bristol Meyers Squibb and Bayer Healthcare Pharmaceuticals; and received honoraria from Amgen.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
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