Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
Clin Colorectal Cancer. 2010 Jan;9(1):22-30. doi: 10.3816/CCC.2010.n.003.
The identification of KRAS mutation status as a predictive biomarker for the activity of epidermal growth factor receptor (EGFR) inhibitors in metastatic colorectal cancer has marked a turning point in the use of these agents in the clinic. A wealth of data indicates that patients with wild-type KRAS derive meaningful clinical benefit from cetuximab in first- and second-line settings and beyond, both in combination and as a single agent, and from panitumumab as a single agent in the refractory setting. Patients with KRAS-mutant tumors do not benefit from EGFR inhibition and should not be treated with these agents. KRAS mutation testing should be part of routine standard practice, preferably at the time of diagnosis or early in the course of management. Immediate knowledge of the KRAS mutation status of a tumor allows for the optimal incorporation of anti-EGFR monoclonal antibody (MoAb) therapy where it may be most beneficial for the patient, such as in downstaging regimens outside of the refractory setting where anti-EGFR MoAb therapy is otherwise typically indicated. Available technologies make this test relatively easy to implement; archival paraffin-embedded samples from primary or metastatic sites can be used indistinctly without compromising reliability and without the need for repeated biopsies. Several diagnostic laboratories provide KRAS testing services. This powerful selection tool reduces unnecessary toxicities and costs and should be part of the standard diagnostic workup of any patient.
KRAS 突变状态的鉴定作为预测生物标志物，可预测表皮生长因子受体（EGFR）抑制剂在转移性结直肠癌中的活性，这标志着这些药物在临床上的应用发生了重大转变。大量数据表明，野生型 KRAS 患者从西妥昔单抗的一线和二线治疗及以上、联合治疗和单药治疗中，以及从 panitumumab 的难治性治疗中，获得了有意义的临床获益。KRAS 突变型肿瘤患者不能从 EGFR 抑制中获益，不应使用这些药物治疗。KRAS 突变检测应成为常规标准实践的一部分，最好在诊断时或在管理过程的早期进行。肿瘤 KRAS 突变状态的即时知识可使抗 EGFR 单克隆抗体（MoAb）治疗的最佳应用，例如在难治性治疗以外的降期方案中，否则通常需要使用抗 EGFR MoAb 治疗。现有的技术使这项检测相对容易实施；原发或转移部位的存档石蜡包埋样本可以不影响可靠性地使用，而无需重复活检。有几个诊断实验室提供 KRAS 检测服务。这种强大的选择工具可减少不必要的毒性和成本，应成为任何患者标准诊断评估的一部分。
