NTRK 1,2,3 Rearrangements in Patients With Solid Tumors

Neurotrophic tropomyosin-related kinases (NTRKs, or the commonly used alias TRKs) constitute a receptor tyrosine kinase family of neurotrophin receptors involved in neuronal development, including the growth and function of neuronal synapses and memory development.

NTRK1/2/3 gene fusions have emerged as new targets for cancer therapy as they can be successfully inhibited by targeted kinase inhibitors. Several compounds targeting TRKs are currently being explored in clinical trials and, notably, one of these compounds, larotrectinib (VITRAKVI®), has received accelerated approval by the United States Food and Drug Administration (FDA) for adult and paediatric solid tumours with a NTRK fusion without known resistance mutations. In addition, entrectinib has received breakthrough designation status by the United States FDA for the treatment of cancers types harbouring NTRK fusions. Hence, there is an active interest in clinical oncology for NTRK fusions, which has prompted an urgent need to define the routine diagnostic test to identify gene fusions as a companion diagnostic method to support clinical decision in this context. Irrespective of the method adopted for NTRK detection, high activity of anti-NTRK agents and therefore the necessity to guarantee these agents to all NTRK+ patients, strongly supports a NTRK screening program for patients with cancer.