title: Development of personalized treatments in lung cancer: focusing on theEGFRmutations and beyond.
abstract: Lung cancers withepidermal growth factor receptor(EGFR) gene mutation account for ∼40% of adenocarcinoma in East Asians and ∼15% of that in Caucasians, which makes them one of the most common molecularly defined lung cancer subsets. The role ofEGFRmutation as a strong predictive biomarker of response to EGFR-tyrosine kinase inhibitors (TKIs) was finally confirmed by the biomarker analysis of Iressa Pan-Asian Study (IPASS). Since the 2004 discovery ofEGFRmutation in lung cancer, theEGFRmutation and EGFR-TKI treatment have been widely studied. These include characteristics of lung cancers withEGFRmutations; clinical efficacies and adverse effects of EGFR-TKIs in patients withEGFR-mutated lung cancers; development of novel EGFR-TKIs that may prolong progression-free survival of these patients or overcome resistance to first-generation EGFR-TKIs (gefitinib and erlotinib); optimal treatment schedules for EGFR-TKIs to delay emergence of resistance; molecular mechanisms of acquired resistance to EGFR-TKIs; treatment strategies after patients acquire resistance to EGFR-TKIs; and predictive biomarkers for EGFR-TKIs among patients withEGFR-mutated lung cancers. Some of these results are widely accepted, while others are apparent only in cell line models, preclinical animal models, or retrospective analyses (and sometimes conflict with each other). In this review, we summarize accumulated reports from the past decade, especially focusing on unanswered but important clinical questions in treating patients withEGFR-mutated lung cancers.
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Japan; Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Suda
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, Osaka-Sayama, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mitsudomi
keywords: acquired resistance; adjuvant therapy; epidermal growth factor receptor mutation; molecular target; personalized therapy; predictive biomarkers