[The mechanisms of resistance to EGFR-TKIs and challenges to overcome resistance in EGFR mutant non-small cell lung cancer].
Somatic activating mutations in the epidermal growth factor receptor (EGFR) gene were first identified in 2004 from tumor tissues of non-small cell lung cancer (NSCLC) patients and pulmonary adenocarcinoma cell lines. Although pulmonary adenocarcinoma patients harboring EGFR mutations have increased sensitivity to EGFR tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, the primary and acquired resistant cases remain major clinical problems. Therapeutic strategies for such oncogene-driven carcinomas were intensively investigated at both the clinical and preclinical levels. In this review, we focused on one particular molecularly-defined subset of NSCLC that harbors activating mutations in the EGFR gene. We summarized the rational dissection of the mechanisms of drug sensitivity and resistance to EGFR-TKIs, and the promising molecular-centric strategies for further improving the outcomes of NSCLC patients with EGFR activating mutations.
Institute of Molecular Oncology, Showa University, Tokyo, Japan.
Toshimitsu
T
Yamaoka
Tohru
T
Ohmori
D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*
D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors