Anti-angiogenic therapy: Rationale, challenges and clinical studies

摘要: Physiological angiogenesis occurs during embryogenesis, wound healing and reproductive functions in adults. Abnormal takes place certain chronic diseases (diabetes, psoriasis, rheumatoid arthritis, etc.) tumours. Genetic changes local stresses including hypoxia, glucose deprivation oxidative stress play a pivotal role switch, which is necessary for tumour development rate-limiting progression. Angiogenesis tightly regulated by pro- anti-angiogenic growth factors with series of complex interrelated steps. Activated endothelial cells (ECs) migrate as solid cord and, subsequently, form lumina; the sprout tips then anastomose to vessel loops or networks. One final events laying down basement membrane structural support pericytes. The molecular alterations that sustain represent novel targets rationally designed anti-cancer treatment strategies. Inhibition presents advantages on conventional therapies, such direct accessibility from circulation, potential low rate drug resistance related genetic stability ECs. Certain compounds were found have potent anticancer property vivo experimental studies. Nevertheless, contrast preclinical studies, first generation drugs tested clinical trials shown moderate activity advanced disease partly due suboptimal schedules therapy biases study design.