, Volume 29, Issue 1, pp 49-60

Biological and clinical significance of KRAS mutations in lung cancer: an oncogenic driver that contrasts with EGFR mutation

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Abstract

KRAS and epidermal growth factor receptor (EGFR) are the two most frequently mutated proto-oncogenes in adenocarcinoma of the lung. The occurrence of these two oncogenic mutations is mutually exclusive, and they exhibit many contrasting characteristics such as clinical background, pathological features of patients harboring each mutation, and prognostic or predictive implications. Lung cancers harboring the EGFR mutations are remarkably sensitive to EGFR tyrosine kinase inhibitors such as gefitinib or erlotinib. This discovery has dramatically changed the clinical treatment of lung cancer in that it almost doubled the duration of survival for lung cancer patients with an EGFR mutation. In this review, we describe the features of KRAS mutations in lung cancer and contrast these with the features of EGFR mutations. Recent strategies to combat lung cancer harboring KRAS mutations are also reviewed.

Supported in part by a Grant-in-Aid for Scientific Research (B) from the Japan Society for the Promotion of Science (20903076) and grant from the Kobayashi Institute for Innovative Cancer Chemotherapy