Institute of Cancer Sciences and Christie Hospital, University of Manchester, Manchester, UK.
Biological Sciences Platform, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
Lancet. 2016 Jul 30;388(10043):518-29. doi: 10.1016/S0140-6736(15)01088-0. Epub 2016 Feb 5.
Angiogenesis, the formation of new blood vessels from pre-existing vessels, has been validated as a target in several tumour types through randomised trials, incorporating vascular endothelial growth factor (VEGF) pathway inhibitors into the therapeutic armoury. Although some tumours such as renal cell carcinoma, ovarian and cervical cancers, and pancreatic neuroendocrine tumours are sensitive to these drugs, others such as prostate cancer, pancreatic adenocarcinoma, and melanoma are resistant. Even when drugs have yielded significant results, improvements in progression-free survival, and, in some cases, overall survival, are modest. Thus, a crucial issue in development of these drugs is the search for predictive biomarkers-tests that predict which patients will, and will not, benefit before initiation of therapy. Development of biomarkers is important because of the need to balance efficacy, toxicity, and cost. Novel combinations of these drugs with other antiangiogenics or other classes of drugs are being developed, and the appreciation that these drugs have immunomodulatory and other modes of action will lead to combination regimens that capitalise on these newly understood mechanisms.
血管生成,即从先前存在的血管中形成新的血管,已通过随机试验在几种肿瘤类型中得到验证,将血管内皮生长因子(VEGF)途径抑制剂纳入治疗武器库。尽管某些肿瘤,如肾细胞癌、卵巢癌和宫颈癌以及胰腺神经内分泌肿瘤对这些药物敏感,但其他肿瘤,如前列腺癌、胰腺腺癌和黑色素瘤则具有耐药性。即使这些药物取得了显著的效果,在无进展生存期方面的改善,以及在某些情况下,总生存期方面的改善也是适度的。因此,开发这些药物的一个关键问题是寻找预测生物标志物——在开始治疗之前预测哪些患者将受益,哪些患者不会受益的测试。生物标志物的开发很重要,因为需要平衡疗效、毒性和成本。这些药物与其他抗血管生成药物或其他类别的药物的新组合正在开发中,并且人们认识到这些药物具有免疫调节和其他作用模式,这将导致联合治疗方案利用这些新的理解机制。
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