Division of Thoracic Surgery, Department of Surgery, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, 589-8511, Japan,
Arch Toxicol. 2015 Aug;89(8):1227-40. doi: 10.1007/s00204-015-1524-7. Epub 2015 May 17.
Lung cancers with an epidermal growth factor receptor (EGFR) gene mutation account for ~40 % of adenocarcinomas in East Asians and ~15 % of those in Caucasians and African Americans, which makes them one of the most common molecularly defined lung cancer subsets. The discriminative clinical and pathological features of lung cancers with EGFR mutations have been intensively studied, and the predictive role of an EGFR mutation for treatment with EGFR tyrosine kinase inhibitors (EGFR-TKIs) is well established. However, controversial issues remain regarding the clinical and therapeutic implications of EGFR mutations in lung cancers. These include the prognostic impact of the EGFR mutation, its predictive implication for successful treatment with anticancer agents other than EGFR-TKIs, appropriate cytotoxic agents for lung cancers with this mutation, and the chemosensitivity of EGFR-mutation-positive lung cancers after acquisition of resistance to EGFR-TKIs. In this review, we discuss these unanswered but important questions, referring to in vitro studies, basic research, retrospective analyses, and the results of phase III clinical trials.
具有表皮生长因子受体 (EGFR) 基因突变的肺癌约占东亚人群中腺癌的 40%，占白种人和非裔美国人中腺癌的 15%，使其成为最常见的分子定义肺癌亚型之一。EGFR 基因突变的肺癌的鉴别临床和病理特征已得到深入研究，EGFR 突变对 EGFR 酪氨酸激酶抑制剂 (EGFR-TKIs) 治疗的预测作用已得到充分证实。然而，EGFR 突变在肺癌中的临床和治疗意义仍存在争议。这些问题包括 EGFR 突变的预后影响、其对 EGFR-TKIs 以外的抗癌药物成功治疗的预测意义、具有这种突变的肺癌的合适细胞毒性药物，以及对 EGFR-TKIs 耐药后 EGFR 突变阳性肺癌的化疗敏感性。在这篇综述中，我们参考体外研究、基础研究、回顾性分析和 III 期临床试验的结果，讨论了这些未解决但重要的问题。
