Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer
Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer
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DOI：
10.1200/jco.2006.07.3585
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发表时间：
2007-02-10
影响因子：
45.3
通讯作者：
Haber, Daniel A.
中科院分区：
文献类型：
--
作者：
Sequist, Lecia V.;Bell, Daphne W.;Haber, Daniel A.
在过去的5年中，表皮生长因子受体（EGFR）已成为肿瘤学药物开发的最重要靶点之一。靶向EGFR外部结构域的单克隆抗体与化疗和/或放疗联合治疗结直肠癌和头颈癌已显示出临床获益。抑制EGFR酪氨酸激酶（TK）结构域的小分子已成为治疗非小细胞肺癌（NSCLC）的关键新武器。发现TK结构域中的突变与EGFR TK抑制剂（TKI）的显著和持续反应相关，允许设计试验来测试这些药物作为潜在的一线治疗，并为基因型导向靶向治疗的未来提供了一个迷人的窗口。最近的进展，了解获得性耐药的生物学基础，这些药物有很大的潜力，以提高这类药物的临床疗效。本文综述了EGFR在NSCLC中的生物学、EGFR TKI治疗获益的临床和分子预测因子、患者特异性分子谱的使用以及临床和基础科研的未来方向。
In the last 5 years the epidermal growth factor receptor ( EGFR) has emerged as one of the most important targets for drug development in oncology. Monoclonal antibodies targeting the external domain of EGFR have been shown to have clinical benefit in colorectal and head and neck cancer when combined with chemotherapy and/or radiation. Small molecules that inhibit the tyrosine kinase (TK) domain of EGFR have become critical new weapons in the treatment of non-small-cell lung cancer (NSCLC). The discovery that mutations in the TK domain are associated with dramatic and sustained responses to EGFR TK inhibitors (TKIs) has allowed the design of trials to test these agents as potential first-line therapies and has provided a fascinating window into the future of genotype-directed targeted therapy. Recent advances in understanding the biologic basis of acquired resistance to these agents have great potential to improve the clinical effectiveness of this class of drugs. This review summarizes the biology of EGFR in NSCLC, the clinical and molecular predictors of benefit from treatment with EGFR TKIs, the use of patient-specific molecular profiling, and future directions of clinical and basic scientific research.