New Targets in Lung Cancer (Excluding EGFR, ALK, ROS1)

Abstract

Purpose of review: Over the last two decades, the identification of targetable oncogene drivers has revolutionized the therapeutic landscape of non-small cell lung cancer (NSCLC). The extraordinary progresses made in molecular biology prompted the identification of several rare molecularly defined subgroups. In this review, we will focus on the novel and emerging actionable oncogenic drivers in NSCLC.

Recent findings: Recently, novel oncogene drivers emerged as promising therapeutic targets besides the well-established EGFR mutations, and ALK/ROS1 rearrangements, considerably expanding the list of potential exploitable genetic aberrations. However, the therapeutic algorithm in these patients is far less defined. The identification of uncommon oncogene drivers is reshaping the diagnostic and therapeutic approach to NSCLC. The introduction of novel highly selective inhibitors is expanding the use of targeted therapies to rare and ultra-rare subsets of patients, further increasing the therapeutic armamentarium of advanced NSCLC.

Keywords: Afatinib; BLU-667; BRAF; Capmatinib; Entrectinib; Gene fusion; LOXO-292; Larotrectinib; MET; NRG1; NSCLC; NTRK; New targets; Oncogene driver; Poziotinib; Pralsetinib; Pyrotinib; RET; Rearrangement; Selpercatinib; T-DM1; Tepotinib.