, Volume 79, Issue 12, pp 1277–1286 | Cite as

Targeting ROS1 Rearrangements in Non-small Cell Lung Cancer: Crizotinib and Newer Generation Tyrosine Kinase Inhibitors

  • Tessa A. Morris
  • Christine Khoo
  • Benjamin J. SolomonEmail author
Leading Article


ROS1 gene rearrangements exist in 1–2% of non-small cell lung cancers, typically occurring in younger, never or light smokers with adenocarcinoma. ROS1 gene fusions are potent oncogenic drivers, the presence of which results in the susceptibility of tumours to ROS1-targeted therapy. Crizotinib was the first tyrosine kinase inhibitor to demonstrate activity in ROS1-rearranged lung cancer, and remains the recommended first-line therapy for patients with advanced ROS1-rearranged non-small cell lung cancer. Despite excellent initial responses to crizotinib, the majority of patients develop disease progression, which may be intracranial or extracranial. Identification of resistance mechanisms to crizotinib, and newer generation tyrosine kinase inhibitors with increased potency against ROS1 and ROS1-resistance mutations, and improved intracranial activity are under evaluation in clinical trials. In this review, we discuss ROS1 rearrangements in non-small cell lung cancer, and provide an update on targeting ROS1-rearranged non-small cell lung cancer with crizotinib and newer generation tyrosine kinase inhibitors.


Compliance with Ethical Standards


No external funding was received for the preparation of this article.

Conflict of interest

Tessa A. Morris and Christine Khoo have no conflicts of interest that are directly relevant to the content of this article. Benjamin J. Solomon has served on advisory boards and received honoraria from Pfizer, Roche-Genentech, Novartis, AstraZeneca, Merck, Bristol Myers Squibb, Loxo Oncology and Gritstone Oncology.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Tessa A. Morris
    • 1
  • Christine Khoo
    • 2
  • Benjamin J. Solomon
    • 1
    • 3
    Email author
  1. 1.Department of Medical OncologyPeter MacCallum Cancer CentreMelbourneAustralia
  2. 2.Department of PathologyPeter MacCallum Cancer CentreMelbourneAustralia
  3. 3.Sir Peter MacCallum Department of OncologyUniversity of MelbourneParkvilleAustralia

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