Ciblage de MET, T790M et ROS1

In the last decade, the characterization of non-small-cell lung cancer into subtypes based on genotype has resulted in dramatic improvements in outcome in selected patient subgroups. Targeted agents that inhibit EGFR or ALK are approved for the treatment of NSCLC harboring genetic alterations of these genes. Similar to EGFR and ALK, those patients that harbor recently discovered molecular abnormalities such as ROS1 fusion or Met mutated or amplified were found to respond to targeted therapies. The most common mechanism of resistance to first-generation EGFR tyrosine kinase inhibitors is a new mutation T790M located in the exon 20 of EGFR. Encouraging results are observed with mutant-selective EGFR tyrosine kinase inhibitors, raising the possibility of overcoming drug resistance to erlotinib or gefitinib. This review provides an overview of the key developments in the treatment of NSCLC, and discusses potential strategies to further optimize therapy by targeting disease subtypes.