Edelman Martin J
Department of Medical Hematology/Oncology, University of Maryland Greenebaum Cancer Center, Baltimore, MD 21201, USA.
Semin Oncol. 2005 Dec;32(6 Suppl 10):S3-8. doi: 10.1053/j.seminoncol.2005.10.002.
Within the past 2 years, epidermal growth factor receptor (EGFR) inhibitors have moved from experimental agents to approved drugs for the management of advanced non-small cell lung cancer (NSCLC). This evolution has been accompanied by dramatic improvements in the understanding of how these drugs work and the clinical populations that may benefit. The identification of mutations in the ATP-binding domain of the EGFR that predict for dramatic responses introduces the possibility of truly individualized therapy in a subset of advanced NSCLC patients. The fact that these mutations may be more prevalent in certain patient populations, including patients of Asian ethnicity, female gender, and never-smoker status, raises intriguing questions regarding the pathogenesis of lung cancer. Another emerging area in the understanding of these agents revolves around the clinical observation that acneform rash may predict for superior outcome and the question of how this rash may relate to polymorphisms in the EGFR gene. EGFR polymorphisms, both germline and somatic, may be a relevant factor in unraveling the mechanism of the benefit of erlotinib in patients who do not harbor an EGFR ATP-binding site mutation. Numerous questions have arisen regarding how to best incorporate EGFR-targeted agents into patient management, as well as the role of the clinical laboratory in these decisions and the design of future trials.
在过去两年中，表皮生长因子受体（EGFR）抑制剂已从实验性药物转变为用于治疗晚期非小细胞肺癌（NSCLC）的获批药物。这一进展伴随着对这些药物作用机制以及可能受益的临床人群的理解取得了显著进步。EGFR的ATP结合域中预测显著反应的突变的鉴定，为一部分晚期NSCLC患者真正实现个体化治疗带来了可能性。这些突变在某些患者群体中可能更为普遍，包括亚裔、女性和从不吸烟的患者，这引发了关于肺癌发病机制的有趣问题。在对这些药物的理解方面，另一个新兴领域围绕临床观察展开，即痤疮样皮疹可能预示着更好的预后，以及这种皮疹与EGFR基因多态性之间的关系问题。EGFR多态性，包括种系和体细胞多态性，可能是阐明厄洛替尼在未携带EGFR ATP结合位点突变的患者中获益机制的一个相关因素。关于如何最佳地将EGFR靶向药物纳入患者管理，以及临床实验室在这些决策和未来试验设计中的作用，已经出现了许多问题。
