Amgen, Inc, Thousand Oaks, CA 91320-1799, USA.
Am J Ther. 2009 Nov-Dec;16(6):554-61. doi: 10.1097/MJT.0b013e318199fa17.
Inhibitors of the epidermal growth factor receptor (EGFR) have demonstrated promising potential in the treatment of advanced colorectal cancer. However, a proportion of patients do not respond to therapy with EGFR inhibitors, and therefore, there has been interest in identifying those patients most likely to benefit from therapy with these agents. KRAS, a member of the RAS family of signaling proteins, plays an important role in EGFR-mediated regulation of cellular proliferation and survival. Although there is still some debate regarding the prognostic importance of KRAS mutations in patients with metastatic colorectal cancer, several recent phase 2 and 3 studies have identified the presence of mutations at codons 12 and 13 of KRAS as predictors of poor response to the anti-EGFR monoclonal antibodies panitumumab and cetuximab. Patients with wild-type KRAS were found to have significantly better progression-free survival, overall survival, and/or objective response rate compared with patients harboring KRAS mutations. As a result, there has been growing interest in the development of KRAS mutational status as a biomarker for predicting patient response to EGFR-targeted therapy. Screening colorectal tumors for the absence of KRAS mutations may help identify patients most likely to benefit from anti-EGFR therapies.
表皮生长因子受体 (EGFR) 的抑制剂在治疗晚期结直肠癌方面显示出了巨大的潜力。然而，一部分患者对 EGFR 抑制剂治疗没有反应，因此，人们一直致力于寻找那些最有可能从这些药物治疗中获益的患者。KRAS 是 RAS 家族信号蛋白的成员，在 EGFR 介导的细胞增殖和存活调节中发挥着重要作用。尽管关于转移性结直肠癌患者 KRAS 突变的预后意义仍存在一些争议，但最近的几项 2 期和 3 期研究已经确定了 KRAS 密码子 12 和 13 突变是对抗 EGFR 单克隆抗体 panitumumab 和 cetuximab 反应不良的预测因子。与携带 KRAS 突变的患者相比，KRAS 野生型患者的无进展生存期、总生存期和/或客观缓解率显著提高。因此，人们越来越关注 KRAS 突变状态作为预测患者对 EGFR 靶向治疗反应的生物标志物的发展。筛选结直肠肿瘤中是否存在 KRAS 突变可能有助于确定最有可能从抗 EGFR 治疗中获益的患者。
