Oncogenic driver mutations in lung cancer

Susan Y Luo, David CL Lam

Lung cancer is a heterogeneous and complex disease. Genomic and transcriptomic profiling of lung cancer not only further our knowledge about cancer initiation and progression, but could also provide guidance on treatment decisions. The fact that targeted treatment is most successful in a subset of tumors indicates the need for better classification of clinically related molecular tumor phenotypes based on better understanding of the mutations in relevant genes, especially in those oncogenic driver mutations. EGFR gene mutations, KRAS gene mutations, EML4-ALK rearrangements and altered MET signaling are widely recognized alterations that play important roles in both the biological mechanisms and the clinical sensitivity to treatment in lung cancer. In this article, we reviewed the discovery of the clinical values of these oncogenic driver mutations and the clinical studies revealing the prognostic and predictive values of these biomarkers for clinical sensitivity and resistance to anti-EGFR therapy or other targeted therapies. These form the basis of personalized treatment in lung cancer based on biomarker profiles of individual tumor, leading to therapeutic advancement and betterment.