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Department of Life, Health & Chemical Sciences, The Open University, Walton Hall, Milton Keynes MK7 6AA, UK.
Future Med Chem. 2016;8(4):443-62. doi: 10.4155/fmc.16.6. Epub 2016 Mar 2.
Angiogenesis is a process essential for tumor growth and metastasis. Inhibition of angiogenesis as an anticancer strategy has shown only moderately improved results and is beset with practical limitations, despite theoretical therapeutic advantages. Inevitably resistance develops, through redundancy of signaling pathways and selection for subclonal populations adapted for hypoxic conditions, with more invasive phenotypes. Antiangiogenic-targeted therapies may find improved efficacy in combination therapies; with others in this class, that directly or indirectly target separate pathways or different components of the same pathway, or with a separate class of tumor vasculature-disrupting agents. This review discusses the challenges and strategies for optimization of combination therapies including metronomic administration of drugs and the need for suitable prognostic and surrogate response biomarkers.
血管生成是肿瘤生长和转移所必需的过程。尽管抗血管生成作为一种抗癌策略在理论上具有治疗优势，但目前其效果仅适度改善，且存在实际局限性。由于信号通路的冗余以及对适应低氧条件的亚克隆群体的选择，不可避免地会产生耐药性，这些亚克隆群体具有更具侵袭性的表型。抗血管生成靶向疗法在联合治疗中可能会有更高的疗效；可与该类中的其他疗法联合，这些疗法直接或间接靶向不同的信号通路或同一信号通路的不同组成部分，或者与另一类肿瘤血管破坏剂联合。本综述讨论了联合治疗优化面临的挑战和策略，包括药物的节律性给药以及对合适的预后和替代反应生物标志物的需求。
