Targeting ROS1 rearrangements in non-small cell lung cancer with crizotinib and other kinase inhibitors

The discovery of molecular subtypes of non-small cell lung cancer (NSCLC) with oncogenic driver mutations and translocations/rearrangements has led to successful development of targeted therapies and improvement in outcomes of advanced lung cancer patients. The frequency of these different subtypes and their clinical impact are illustrated in Figure 1A (1). Of these, drugs have already been approved by regulatory agencies for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 receptor tyrosine kinase (ROS1), and B-RAF proto-oncogene serine/threonine kinase (BRAF) targeted treatments. There are ongoing clinical trials for development of targeted therapies against other activated “driver oncogenes” in NSCLC, including MET proto-oncogene receptor tyrosine kinase (MET), ret proto-oncogene (RET), Erb-B2 receptor tyrosine kinase 2 (ERBB2), and neurotrophic receptor tyrosine kinase 1 (NTRK) among others