Department of Clinical Oncology, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae, Kawasaki, Kanagawa, 2168511, Japan.
Drugs. 2019 Apr;79(6):633-645. doi: 10.1007/s40265-019-01113-0.
The epidermal growth factor receptor (EGFR) and RAS/RAF signaling pathway plays pivotal roles in tumor progression via proliferation, survival, invasion, and immune evasion. Two anti-EGFR monoclonal antibodies, cetuximab and panitumumab, have become essential components in the treatment of patients with metastatic colorectal cancer (mCRC). Treatment with these anti-EGFR antibodies has shown definite benefits when administered in all treatment lines and is strongly recommended as the preferred regimen to prolong survival, especially when administered in the first- and third-lines. Recent efforts have revealed not only mechanisms responsible for resistance to anti-EGFR antibodies, including expanded RAS mutations as a negative predictive biomarker, but also the possibility of continuing anti-EGFR antibody treatment in combination with chemotherapy. Furthermore, the challenges associated with the pharmaceutical development of treatments for patients with mutant-type BRAF mCRC are ongoing. In this review, we provide an overview of the EGFR and RAS/RAF signaling pathway and antitumor activity, focusing on practical aspects such as established treatments including patient selection, treatment strategies, and future perspectives for drug development targeting the EGFR and RAS/RAF signaling pathway.
表皮生长因子受体（EGFR）和 RAS/RAF 信号通路通过增殖、存活、侵袭和免疫逃逸在肿瘤进展中发挥关键作用。两种抗 EGFR 单克隆抗体，西妥昔单抗和帕尼单抗，已成为治疗转移性结直肠癌（mCRC）患者的重要组成部分。在所有治疗线中使用这些抗 EGFR 抗体治疗已显示出明确的益处，并强烈建议将其作为延长生存的首选方案，特别是在一线和三线治疗中。最近的研究不仅揭示了导致对 EGFR 抗体产生耐药的机制，包括扩展的 RAS 突变作为阴性预测生物标志物，还揭示了在联合化疗的情况下继续使用抗 EGFR 抗体治疗的可能性。此外，针对突变型 BRAF mCRC 患者的药物开发所面临的挑战仍在继续。在这篇综述中，我们概述了 EGFR 和 RAS/RAF 信号通路以及抗肿瘤活性，重点介绍了已确立的治疗方法，包括患者选择、治疗策略以及针对 EGFR 和 RAS/RAF 信号通路的药物开发的未来前景。
