Non-small cell lung cancer targetable mutations: present and future

Rapid advances in the utility of molecular testing to identify common and uncommon driver mutations as well as the expeditious rate of drug development have intensified the need to obtain multiplex next generation sequencing from tissue and/or blood at the time of diagnosis in order to determine the most appropriate treatment for patients with advanced lung cancers. In this review, we discuss the currently available investigational targeted therapies for the treatment of sensitizing epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) fusions, ROS proto-oncogene 1 (ROS1) fusions, B-Raf proto-oncogene (BRAF) V600E mutations, and neurotrophin receptor tyrosine kinase (NTRK) fusions. In addition, we have highlighted promising investigational therapies aimed at high level mesenchymal-to- epithelial transition factor (MET) amplifications or exon 14 skipping mutations, EGFR or human epidermal growth factor receptor 2 (HER2) exon 20 insertion mutations, rearranged during transfection (RET) fusions, and Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutations that lend support towards routine testing for these driver mutations as well.