Oncogenic driver mutations in non-small cell lung cancer: Past, present and future

Abstract

Lung cancer, of which non-small lung cancer is the most common subtype, represents the leading cause of cancer related-death worldwide. It is now recognized that a significant proportion of these patients present alterations in certain genes that drive oncogenesis. In recent years, more of these so-called oncogenic drivers have been identified, and a better understanding of their biology has allowed the development new targeted agents. This review aims to provide an update about the current landscape of driver mutation in non-small-cell lung cancer. Alterations in Kirsten rat sarcoma, epidermal growth factor receptor, MET, anaplastic lymphoma kinase, c-ROS oncogene 1, v-raf murine sarcoma viral oncogene homolog B, neurotrophic receptor tyrosine kinase, human epidermal growth factor 2, neuregulin-1 and rearranged during transfection are discussed, as well as agents targeting these alterations. Current standards of treatment as well as promising future strategies are presented. Currently, more than fifteen targeted agents are food and Drug administration-approved for seven oncogenic drivers in non-small-cell lung cancer, highlighting the importance of actively searching for these mutations. Continuous and future efforts made in defining the biology of each of these alterations will help to elucidate their respective resistance mechanisms, and to define the best treatment strategy and therapeutic sequence.

Keywords: Driver mutations; Non-small cell lung cancer; Oncogenes; Targeted agents; Tyrosine kinase inhibitors.

Figure 1

Incidence of oncogenic drivers in non-small cell lung cancer. KRAS: Kirsten rat sarcoma; EGFR: Epidermal growth factor receptor; ALK: Anaplastic lymphoma kinase; HER2: Human epidermal growth factor 2; ROS1: c-ROS oncogene 1; NTRK: Neurotrophic receptor tyrosine kinase; RET: Rearranged during transfection; NRG1: Neuregulin-1.