KRAS Mutations and Sensitivity to Epidermal Growth Factor Receptor Inhibitors in Colorectal Cancer: Practical Application of Patient Selection
KRAS Mutations and Sensitivity to Epidermal Growth Factor Receptor Inhibitors in Colorectal Cancer: Practical Application of Patient Selection
复制标题
DOI：
10.1200/jco.2008.19.8168
复制
发表时间：
2009-03-01
影响因子：
45.3
通讯作者：
Eckhardt, S. Gail
中科院分区：
文献类型：
--
作者：
Jimeno, Antonio;Messersmith, Wells A.;Eckhardt, S. Gail
最近来自几项随机研究的回顾性证据表明，患有 KRAS 基因突变的晚期结直肠癌患者不会从表皮生长因子受体导向的单克隆抗体（例如西妥昔单抗或帕尼单抗）的给药中获益。这是一个范式改变的事件，将对当前和未来的抗癌药物开发产生重大影响。这些结果增加了新型靶向疗法开发中涉及的经济和伦理考虑，并应加强我们对早期开发阶段耐药机制和预测生物标志物的审查。在本文中，我们将回顾现有的临床数据，讨论对结直肠癌未来药物开发的潜在影响，并全面概述 KRAS 突变检测的技术方面。我们特别旨在列举突变检测的可用程序及其主要特征，并从临床可行性的角度对它们进行比较。虽然这些方法的真正特异性和敏感性尚未得到充分表征，但更好地了解测试之间的差异至关重要，以便临床医生和病理学家能够将这种测试完全整合到结直肠癌患者的常规护理中。 J 临床肿瘤杂志 27：1130-1136。 (C) 2009 年美国临床肿瘤学会
Recent retrospective evidence from several randomized studies has established that advanced colorectal cancer patients with tumors harboring a mutation in the KRAS gene do not derive benefit from the administration of epidermal growth factor receptor-directed monoclonal antibodies, such as cetuximab or panitumumab. This represents a paradigm-changing event and will have substantial impact on current and future anticancer drug development. These results add to the economic and ethical considerations involved in the development of novel targeted therapies and should increase our scrutiny of mechanisms of resistance and predictive biomarkers while in earlier developmental stages. In this article we will review the available clinical data, discuss the potential implications for future drug development in colorectal cancer, and provide a comprehensive overview of the technical aspects of KRAS mutation testing. In particular we aimed at enumerating the available procedures for mutation detection and their main characteristics, as well as comparing them from a clinical feasibility standpoint. While the true specificity and sensitivity of these methods have yet to be fully characterized, a better understanding of the differences between tests will be critical so that clinicians and pathologists can fully integrate this testing into the routine care of patients with colorectal cancer. J Clin Oncol 27: 1130-1136. (C) 2009 by American Society of Clinical Oncology