NTRK and NRG1 gene fusions in advanced non-small cell lung cancer (NSCLC)

Abstract

Personalized medicine has revolutionized the therapeutic landscape of most solid tumors, including advanced non-small cell lung cancer (NSCLC), with unprecedented results in molecularly defined patient subgroups. Recently, the identification of rare oncogenic drivers with very low frequency in multiple solid tumors has further changed the drug development process leading to the approval of targeted therapies after only phase I studies and independently of tumor histology. Neurotrophic receptor tyrosine kinase (NTRK) and neuregulin-1 (NRG1) gene fusions represent two of the most compelling examples of tumor agnostic biomarkers and, although uncommon in NSCLC, constitute two clinically relevant subgroups of patients that can derive benefit from matched targeted drugs. Here we provide a comprehensive overview of the biological and clinicopathological characteristics of NRG1- and NTRK-rearranged NSCLC and the available data on therapeutic exploitation of these targets.