The potential of neurotrophic tyrosine kinase (NTRK) inhibitors for treating lung cancer

Expert Opin Investig Drugs. 2016;25(4):385-92. doi: 10.1517/13543784.2016.1152261. Epub 2016 Feb 24.

Abstract

Introduction: Molecular alterations in neurotrophic tyrosine kinase (NTRK) genes have been identified in several solid tumors including lung cancer. Pre-clinical and clinical evidence suggested their potential role as oncogenic drivers and predictive biomarkers for targeted inhibition, leading to the clinical development of a new class of compounds blocking the NTRK molecular pathway, which are currently undner early clinical investigation.

Area covered: This review describes the biology of the NTRK pathway and its molecular alterations in lung cancer. It focuses on the pre-clinical and clinical development of emerging NTRK inhibitors, which have shown very promising activity in early phase I studies.

Expert opinion: Among the several NTRK-inhibitors, entrectinib and LOXO-101 are those in more advanced stage of clinical development. Both agents have shown encouraging activity along with a tolerable safety profile in patients with different solid tumors harboring NTRK-fusions, emerging as new promising therapeutic options for molecularly selected patients with advanced Trk-driven lung cancers. Results from ongoing phase II basket trials are eagerly awaited.

Keywords: NTRK-inhibitors; NTRK1/2/3; TrkA/B/C; lung cancer; targeted therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Lung Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*

Substances

  • Protein Kinase Inhibitors
  • Receptor Protein-Tyrosine Kinases