Oncol Res Treat. 2018;41(4):188-193. doi: 10.1159/000488301. Epub 2018 Mar 23.
Angiogenesis is a hallmark of cancer and is regulated by a balance of pro- and anti-angiogenic factors; among them, the vascular endothelial growth factor (VEGF) is the key angiogenic factor. VEGF plays an important role in colorectal cancer (CRC) biology, and its inhibition by using bevacizumab, an anti-VEGF antibody, proved for the first time to be effective and became indispensable for the treatment of metastatic CRC (mCRC). Several large phase III studies showed also relevant responses and tolerability of other anti-angiogenic drugs such as ramucirumab, aflibercept, and regorafenib, and led to the approval of these therapeutics. Nevertheless, the efficacy of anti-angiogenic therapies is rather limited and the high expectations raised by preclinical studies were not fulfilled in the clinics. Furthermore, to date, no predictive biomarkers for anti-angiogenic agents could be identified and validated. Thus, new mechanisms of action are discussed, such as tumor vasculature normalization to improve the accessibility of tumor tissue by drugs or to promote tumor infiltration by host immune cells. Cellular and molecular studies will be necessary to characterize the dynamic changes of the tumor microenvironment and the vascular architecture in individual patients in order to predict responsiveness to anti-angiogenic therapies. In this review, we tried to highlight the standard of care of using anti-angiogenics in mCRC patients and to provide an outlook on potential new substances and strategies.
血管生成是癌症的一个标志，由促血管生成和抗血管生成因子的平衡调节；其中，血管内皮生长因子（VEGF）是关键的血管生成因子。VEGF 在结直肠癌（CRC）生物学中发挥重要作用，使用抗 VEGF 抗体贝伐珠单抗抑制其活性首次被证明是有效的，并成为转移性 CRC（mCRC）治疗不可或缺的手段。几项大型 III 期研究表明，其他抗血管生成药物，如雷莫芦单抗、阿柏西普和瑞戈非尼，也具有相关的疗效和耐受性，这些药物因此获得批准。然而，抗血管生成疗法的疗效相当有限，临床研究并未满足临床前研究的高期望。此外，迄今为止，尚未确定和验证出针对抗血管生成药物的预测性生物标志物。因此，人们正在讨论新的作用机制，例如肿瘤血管正常化，以提高药物对肿瘤组织的可达性，或促进宿主免疫细胞浸润肿瘤。有必要进行细胞和分子研究，以描述个别患者肿瘤微环境和血管结构的动态变化，从而预测对抗血管生成治疗的反应性。在这篇综述中，我们试图强调在 mCRC 患者中使用抗血管生成药物的标准治疗方法，并展望潜在的新物质和策略。
