Frandsen Sofie, Kopp Sascha, Wehland Markus, Pietsch Jessica, Infanger Manfred, Grimm Daniela
Institute of Biomedicine, Pharmacology, Aarhus University, Wilhelm Meyers Allé 4, DK-8000 Aarhus C, Denmark.
Curr Pharm Des. 2016;22(39):5927-5942. doi: 10.2174/1381612822666160715130419.
Angiogenesis is a mechanism, which tumors use to recruit oxygen and nutrients in order to maintain growth. The vascular endothelial growth factor family is the primary mediator of this process. For the last couple of decades, inhibition of angiogenesis has been the subject of extensive research, but so far anti-angiogenic drugs have only shown a modest effect.
This paper reviews four relevant anti-angiogenic drugs: bevacizumab, ramucirumab, nintedanib and sunitinib. The primary focus will be recent trials investigating the effects of the drugs in lung, breast and gastrointestinal cancers. Furthermore, there will be a discussion of unsolved problems, such as lack of biomarkers, drug resistance, and adverse events, for which a solution is necessary in order to improve the benefit of anti-angiogenic drugs in the future.
Anti-angiogenic therapy is extensively used in the treatment of cancer. There is evidence that drug-induced hypertension serves as a biomarker for a good response to therapy. Currently several possible anti-angiogenic biomarkers are under discussion. Further examples are changes in VEGF or interleukin (IL)-8 polymorphisms, changed plasma levels of VEGF, or tumor microvessel density. To overcome therapyassociated problems, more research for valid biomarkers is necessary. In addition, a strategy to overcome resistance problems and severe adverse events is desirable.
Clinical trials evaluating targeted therapies with specificity for resistance mechanisms are necessary. Moreover, biomarker studies in future clinical investigations are important for the development of the next generation of anti-angiogenic drugs.
血管生成是肿瘤用于募集氧气和营养物质以维持生长的一种机制。血管内皮生长因子家族是这一过程的主要介导者。在过去几十年中,抑制血管生成一直是广泛研究的主题,但迄今为止抗血管生成药物仅显示出适度的效果。
本文综述了四种相关的抗血管生成药物:贝伐单抗、雷莫西尤单抗、尼达尼布和舒尼替尼。主要关注点将是近期研究这些药物在肺癌、乳腺癌和胃肠道癌中作用的试验。此外,还将讨论一些未解决的问题,如缺乏生物标志物、耐药性和不良事件,为了提高未来抗血管生成药物的疗效,必须解决这些问题。
抗血管生成疗法广泛应用于癌症治疗。有证据表明药物性高血压可作为治疗良好反应的生物标志物。目前正在讨论几种可能的抗血管生成生物标志物。其他例子包括血管内皮生长因子(VEGF)或白细胞介素(IL)-8多态性的变化、VEGF血浆水平的改变或肿瘤微血管密度。为了克服与治疗相关的问题,需要对有效的生物标志物进行更多研究。此外,需要一种克服耐药性问题和严重不良事件的策略。
有必要进行评估针对耐药机制具有特异性的靶向治疗的临床试验。此外,未来临床研究中的生物标志物研究对于下一代抗血管生成药物的开发很重要。