Coordination of Clinical Research and Technology Incorporation, National Cancer Institute of Brazil (INCA), Rio de Janeiro, Brazil.
Coordination of Clinical Research and Technology Incorporation, National Cancer Institute of Brazil (INCA), Rio de Janeiro, Brazil.
Cancer Treat Rev. 2014 May;40(4):548-57. doi: 10.1016/j.ctrv.2013.11.009. Epub 2013 Dec 6.
Although the inhibition of angiogenesis is an established modality of cancer treatment, concerns regarding toxicity and drug resistance still constitute barriers to be overcome. For almost a decade since the approval of bevacizumab in 2004, the efforts on antiangiogenic therapeutics have been mainly focused in inhibiting the VEGF pathway. The ongoing understanding of the complexity of the angiogenic process has broadened the spotlight to include concurrent and downstream players to the list of targeted inhibitors. In this review, we summarize the currently existing and the promising antiangiogenic treatments, envisioning an apparent evolutionary trend towards the development of angiogenesis inhibitors of three modalities: single-target, multi-target, and broad-spectrum agents. The clinical efficacy and some structural aspects of monoclonal antibodies, small molecules, endogenous and synthetic angiogenesis inhibitors and their molecular targets are discussed, and the targeting of endothelial cells with the use of cytotoxic drugs in a metronomic schedule is appraised. The reader is invited to revisit current expectations about antiangiogenic therapy in an attempt to set consistent clinical endpoints from which patients could gain real and lasting clinical benefits.
尽管抑制血管生成是癌症治疗的一种既定方式，但毒性和耐药性问题仍然是需要克服的障碍。自 2004 年贝伐单抗获得批准以来，近十年来，抗血管生成治疗的重点主要集中在抑制 VEGF 通路。对血管生成过程复杂性的不断认识，将协同作用和下游靶点纳入了靶向抑制剂的范畴。在这篇综述中，我们总结了目前现有的有前途的抗血管生成治疗方法，设想了血管生成抑制剂朝着三种方式发展的明显趋势：单靶点、多靶点和广谱制剂。讨论了单克隆抗体、小分子、内源性和合成血管生成抑制剂及其分子靶点的临床疗效和一些结构方面，评估了在节拍方案中使用细胞毒性药物靶向内皮细胞的效果。我们邀请读者重新审视当前对抗血管生成治疗的期望，努力设定一致的临床终点，使患者获得真正和持久的临床获益。
