Changing the Therapeutic Landscape in Non-small Cell Lung Cancers: the Evolution of Comprehensive Molecular Profiling Improves Access to Therapy

Abstract

Targeting genomic alterations has led to a paradigm shift in the treatment of patients with lung cancer. In an effort to better identify potentially actionable alterations that may predict response to FDA-approved and or investigational therapies, many centers have migrated towards performing targeted exome sequencing in patients with stage IV disease. The implementation of next-generation sequencing (NGS) in the evaluation of tumor tissue from patients with NSCLC has led to the discovery of targetable alterations in tumors that previously had no known actionable targets by less comprehensive profiling. An improved understanding of the molecular pathways that drive oncogenesis in NSCLC and a revolution in the technological advances in NGS have led to the development of new therapies through biomarker-driven clinical trials. This review will focus on the advances in molecular profiling that continue to fuel the revolution of precision medicine, identifying targets such as MET exon 14 skipping alterations and select recurrent gene alterations with increasing frequency.

Keywords: MET exon 14 skipping alteration; Molecular diagnostics; NTRK fusion; Next-generation sequencing (NGS); Non-small cell lung cancer (NSCLC); Precision medicine; RNA sequencing; Targeted therapy.