Jimeno Antonio, Messersmith Wells A, Hirsch Fred R, Franklin Wilbur A, Eckhardt S Gail
Medical Oncology Division, PO Box 6511, MS 8117, Aurora, CO, 80045, USA.
J Clin Oncol. 2009 Mar 1;27(7):1130-6. doi: 10.1200/JCO.2008.19.8168. Epub 2009 Jan 5.
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.
最近来自几项随机研究的回顾性证据表明，患有KRAS基因突变肿瘤的晚期结直肠癌患者无法从给予表皮生长因子受体导向的单克隆抗体（如西妥昔单抗或帕尼单抗）中获益。这是一个改变范式的事件，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治疗开发中涉及的经济和伦理考量，并且应该在早期开发阶段提高我们对耐药机制和预测性生物标志物的审查。在本文中，我们将回顾现有的临床数据，讨论对未来结直肠癌药物开发的潜在影响，并全面概述KRAS突变检测的技术方面。特别是，我们旨在列举可用的突变检测程序及其主要特征，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完全明确，但更好地了解检测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检测完全纳入结直肠癌患者的常规护理中。
