Targeting oncogenic drivers in lung cancer: Recent progress, current challenges and future opportunities

• Published in: Pharmacology & therapeutics (Oxford) Vol. 193; pp. 20 - 30
• Main Authors: Yoda, Satoshi, Dagogo-Jack, Ibiayi, Hata, Aaron N.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.01.2019
• Subjects: ALK; Anaplastic Lymphoma Kinase - genetics; Animals; BRAF; Carcinogenesis; EGFR; ErbB Receptors - genetics; Humans; Immunotherapy; Lung Neoplasms - genetics; Lung Neoplasms - therapy; Molecular Targeted Therapy; NSCLC; Proto-Oncogene Proteins; ROS1; Targeted therapy; ALK; RET; FDA; 19 Del; NSCLC; Targeted therapy; CNS; BRAF; L858R; TRK; EGFR; ORR; TKI; PD-L1; KRAS; PFS; ROS1; MET; PD-1
• ISSN: 0163-7258; 1879-016X
• DOI: 10.1016/j.pharmthera.2018.08.007

Targeted therapies have changed the landscape of treatments for non-small cell lung cancer (NSCLC). Specific targeted therapies have been approved for NSCLC patients harboring genetic alterations in four oncogenes, and agents targeting additional oncogenic drivers are under investigation. Standard first-line chemotherapy has been supplanted by these targeted therapies due to superior efficacy and lower toxicity. Despite excellent response rates and durable responses in some cases, most patients experience relapse within a few years due to the development of acquired drug resistance. Next generation targeted therapies are being developed to overcome drug resistance and extend the duration of therapy. In this review, we summarize the current treatment strategies for the major targetable oncogenic mutations/alterations in NSCLC and discuss the mechanisms leading to acquired drug resistance.