Roswell Park Cancer Institute, Elm & Carlton Streets, Buffalo, NY 14263, USA.
J Gastrointest Oncol. 2013 Jun;4(2):231-8. doi: 10.3978/j.issn.2078-6891.2013.008.
Angiogenesis plays an important role in colorectal carcinogenesis and approaches targeting the vascular growth factor receptor (VEGF) signaling such as bevacizumab yielded significant survival improvement for metastatic colorectal cancer patients. Recent evidence demonstrated the benefit of continuing angiogenic suppression after first-progression following bevacizumab-containing cytotoxic regimen though no benefit was observed with the use of bevacizumab in adjuvant setting. Aflibercept, a soluble fusion protein with high affinity for VEGF-A, -B and PlGF, administered in combination with irinotecan-containing regimen improved the survival of metastatic colorectal cancer patients in second-line setting (VELOUR trial). Regorafenib, a small molecule multikinase inhibitor against various pro-angiogenic and -proliferation targets, improved the survival of metastatic colorectal cancer patients who had progressed on all standard therapy. These developments had renewed enthusiasm in the field and the role of aflibercept and regorafenib in other treatment settings will continue to be defined by on-going and future clinical trials. As other anti-angiogenic approaches are being tested clinically, other novel non-angiogenic targets deserve to be evaluated in our effort to improve the outcome of colorectal cancer patients.
血管生成在结直肠癌的发生发展中起着重要作用，针对血管生长因子受体（VEGF）信号的治疗方法，如贝伐珠单抗，已显著改善转移性结直肠癌患者的生存。最近的证据表明，在贝伐珠单抗联合细胞毒性方案治疗后首次进展时继续进行血管生成抑制是有益的，但在辅助治疗中使用贝伐珠单抗并没有观察到获益。阿柏西普是一种与 VEGF-A、-B 和 PlGF 具有高亲和力的可溶性融合蛋白，与含伊立替康的方案联合使用可改善二线转移性结直肠癌患者的生存（VELOUR 试验）。瑞戈非尼是一种针对多种促血管生成和增殖靶点的小分子多激酶抑制剂，可改善所有标准治疗进展后的转移性结直肠癌患者的生存。这些进展重新激发了该领域的热情，阿柏西普和瑞戈非尼在其他治疗环境中的作用将继续通过正在进行和未来的临床试验来定义。随着其他抗血管生成方法在临床上的测试，其他新的非血管生成靶点值得在我们努力改善结直肠癌患者预后的过程中进行评估。
