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: Non-small cell lung cancer, Driver mutations, Tyrosine kinase inhibitors, Targeted agents, Oncogenes

Core Tip: We have reviewed the current literature about the impact of detecting oncogenic mutations in non-small cell lung cancer (NSCLC). Over the years, the adoption of next generation sequencing has rendered it easier to determine and detect possible oncogenic driver mutations, leading to the development of several targeted therapies. The clinical impact and benefit for patients is important in terms of quality and quantity of life. These therapies are more effective than standard chemotherapy treatment. We have reviewed the data to explain what has been done, is ongoing and shall be done in the future for patients with oncogene-driven NSCLC.