ROS1-rearranged Non-small Cell Lung Cancer

Thorac Surg Clin. 2020 May;30(2):147-156. doi: 10.1016/j.thorsurg.2020.01.007.

Abstract

ROS1-rearranged non-small cell lung cancer (NSCLC) makes up approximately 1% to 2% of all NSCLC, is oncogenically driven by a constitutively activated ROS1 kinase paired with certain fusion partners, and can be detected by several different assays. These patients are initially treated with tyrosine kinase inhibitors (TKIs), which target the activated ROS1 kinase. Eventually these tumors develop resistance to initial TKI treatment through secondary kinase mutations that block TKI binding or activation of bypass signaling pathways, which subvert ROS1 as the driver of the malignancy. Investigation of several TKIs that have shown efficacy in secondary resistant patients is underway.

Keywords: Lung cancer; Non–small cell lung cancer (NSCLC); ROS1 fusion; ROS1 inhibitor; ROS1 rearrangement; Resistance mechanism; Targeted therapy; Tyrosine kinase inhibitor (TKI).

Publication types

  • Review

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Drug Resistance, Neoplasm / physiology
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Mutation
  • Pharmacogenetics
  • Protein Kinase Inhibitors / pharmacology*
  • Protein-Tyrosine Kinases* / antagonists & inhibitors
  • Protein-Tyrosine Kinases* / genetics
  • Proto-Oncogene Proteins* / antagonists & inhibitors
  • Proto-Oncogene Proteins* / genetics

Substances

  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • ROS1 protein, human