The Molecular Pharmacology and Therapeutics of Angiogenesis

Abstract

Angiogenesis is the formation of new vasculature on top of the pre-existing ones, which is critical during the species’ lifespan. It is responsible for delivering oxygen and nutrients to metabolically active tissues, therefore playing an essentialrole in physiological conditions, such as wound healing and pathological circumstances, like malignancies. Althoughsharing similar characteristics, the blood vessels in pathological angiogenesis develop irregularly and disorganizedly.Therefore, the leakage of materials from blood vessels is familiar in abnormal angiogenesis, which may result inmuch higher interstitial pressure than internal pressure. Whether the angiogenesis is physiological or pathological,the proliferation of normal dormant endothelial cells is an essential requirement. Additionally, angiogenesis is alsoinitiated by vascular endothelial growth factor A (VEGF-A) interacting with the vascular endothelial growth factorreceptor 2 (VEGFR2) or the co-receptor neuropilin-1 (NRP-1). The Vegfa gene can be spliced in many ways, creatingnumerous VEGF-A isoforms, each with unique interactions with VEGFR2. Several drugs have been approved as thefirst- or second-line of angiogenesis, thereby preventing cancer progression. The widely used is monoclonal antibodies(bevacizumab) and receptor tyrosine kinase inhibitor (sorafenib and axitinib). However, they lack selectivity and, asa result, are less effective and have considerable adverse effects. As a natural drug, Paclitaxel has an anti-angiogeniceffect in addition to its chemotherapeutic effect. However, different doses of paclitaxel have different anti-angiogenicmechanisms and different effects on different species.