Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Penang 11800, Malaysia.
Faculty of Pharmaceutical Sciences, Government College University, Faisalabad 38000, Pakistan.
Medicina (Kaunas). 2018 Mar 25;54(1):8. doi: 10.3390/medicina54010008.
Deregulated angiogenesis has been identified as a key contributor in a number of pathological conditions including cancer. It is a complex process, which involves highly regulated interaction of multiple signalling molecules. The pro-angiogenic signalling molecule, vascular endothelial growth factor (VEGF) and its cognate receptor 2 (VEGFR-2), which is often highly expressed in majority of human cancers, plays a central role in tumour angiogenesis. Owing to the importance of tumour vasculature in carcinogenesis, tumour blood vessels have emerged as an excellent therapeutic target. The anti-angiogenic therapies have been shown to arrest growth of solid tumours through multiple mechanisms, halting the expansion of tumour vasculature and transient normalization of tumour vasculature which help in the improvement of blood flow resulting in more uniform delivery of cytotoxic agents to the core of tumour mass. This also helps in reduction of hypoxia and interstitial pressure leading to reduced chemotherapy resistance and more uniform delivery of cytotoxic agents at the targeted site. Thus, complimentary combination of different agents that target multiple molecules in the angiogenic cascade may optimize inhibition of angiogenesis and improve clinical benefit in the cancer patients. This review provides an update on the current trend in exploitation of angiogenesis pathways as a strategy in the treatment of cancer.
血管生成失调已被确定为多种病理状况的关键因素,包括癌症。这是一个复杂的过程,涉及多种信号分子的高度调节相互作用。促血管生成信号分子血管内皮生长因子 (VEGF)及其同源受体 2 (VEGFR-2) 在大多数人类癌症中常高度表达,在肿瘤血管生成中发挥核心作用。由于肿瘤血管生成在致癌作用中的重要性,肿瘤血管已成为一个极好的治疗靶点。抗血管生成疗法已被证明通过多种机制抑制实体瘤的生长,阻止肿瘤血管的扩张和肿瘤血管的短暂正常化,从而有助于改善血流,使细胞毒性药物更均匀地输送到肿瘤核心。这还有助于减少缺氧和间质压力,从而降低化疗耐药性,并在靶向部位更均匀地输送细胞毒性药物。因此,互补组合靶向血管生成级联中多种分子的不同药物可能会优化血管生成抑制作用,并提高癌症患者的临床获益。本文综述了利用血管生成途径作为癌症治疗策略的最新趋势。