Merla Amartej, Goel Sanjay
Department of Medicine, Montefiore Medical Center, 111 210th Street, Bronx, NY 10467, USA.
Chemother Res Pract. 2012;2012:387172. doi: 10.1155/2012/387172. Epub 2012 Oct 14.
Colorectal cancer is the second most common malignancy among men and women in the United States, and the 5-year survival rate remains poor despite recent advances in chemotherapy and targeted agents. The mainstay of therapy for advanced disease remains the cytotoxic chemotherapy including 5-FU, irinotecan, and oxaliplatin. The USFDA approval and introduction of targeted therapies, including cetuximab and panitumumab (monoclonal antibodies targeting the epidermal growth factor receptor (EGFR)) and bevacizumab (monoclonal antibody targeting the vascular epithelial growth factor (VEGF)), has improved the median survival of patients with metastatic colorectal cancer to around 24 months. Clearly, better and more efficacious drugs are needed, and target-specific agents remain the future of cancer treatment. On this front, rapid advances are being made, which are likely to change the future of the management of metastatic colorectal cancer. However, absence of specific biomarkers for the use of targeted agents, in the subset of population who will benefit from the treatment, remains a major drawback. In this paper, we review agents that are in phases 1 and 2 clinical development, specifically targeting the EGFR and its subsequent downstream pathways.
结直肠癌是美国男性和女性中第二常见的恶性肿瘤，尽管化疗和靶向药物最近取得了进展，但其5年生存率仍然很低。晚期疾病的主要治疗方法仍然是细胞毒性化疗，包括5-氟尿嘧啶、伊立替康和奥沙利铂。美国食品药品监督管理局（USFDA）批准并引入了靶向治疗药物，包括西妥昔单抗和帕尼单抗（靶向表皮生长因子受体（EGFR）的单克隆抗体）以及贝伐单抗（靶向血管内皮生长因子（VEGF）的单克隆抗体），这将转移性结直肠癌患者的中位生存期提高到了约24个月。显然，需要更好、更有效的药物，而靶向特异性药物仍然是癌症治疗的未来方向。在这方面正在取得快速进展，这可能会改变转移性结直肠癌的治疗前景。然而，在将从治疗中获益的人群亚组中，缺乏用于靶向药物的特异性生物标志物仍然是一个主要缺陷。在本文中，我们综述了处于1期和2期临床开发阶段、专门靶向EGFR及其下游通路的药物。
