Recent Advances in Targeting ROS1 in Lung Cancer

J Thorac Oncol. 2017 Nov;12(11):1611-1625. doi: 10.1016/j.jtho.2017.08.002. Epub 2017 Aug 14.


ROS1 is a validated therapeutic target in NSCLC. In a phase I study, the multitargeted MET proto-oncogene, receptor tyrosine kinase/anaplastic lymphoma kinase/ROS1 inhibitor crizotinib demonstrated remarkable efficacy in ROS1-rearranged NSCLCs and consequently gained approval by the United States Food and Drug Administration and by the European Medicines Agency in 2016. However, similar to other oncogene-driven lung cancers, ROS1-rearranged lung cancers treated with crizotinib eventually acquire resistance, leading to disease relapse. Novel ROS1 inhibitors and therapeutic strategies are therefore needed. Insights into the mechanisms of resistance to ROS1-directed tyrosine kinase inhibitors are now beginning to emerge and are helping to guide the development of new ROS1 inhibitors. This review discusses the biology and diagnosis of ROS1-rearranged NSCLC, and current and emerging treatment options for this disease. Future challenges in the field are highlighted.

Keywords: Crizotinib; Non–small cell lung cancer; ROS1 inhibitor; ROS1 rearrangement; Resistance.

Publication types

  • Review

MeSH terms

  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism


  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • ROS1 protein, human