The Molecular Pharmacology and Therapeutics of Angiogenesis
DOI:
https://doi.org/10.61173/57tgfh39Keywords:
Angiogenesis, Endothelial cells, VEGF, VEGFR, NRP1, Bevacizumab, PaclitaxelAbstract
Angiogenesis is the formation of new vasculature on top of the pre-existing ones, which is critical during the species’ life
span. It is responsible for delivering oxygen and nutrients to metabolically active tissues, therefore playing an essential
role in physiological conditions, such as wound healing and pathological circumstances, like malignancies. Although
sharing 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 in
much 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 also
initiated by vascular endothelial growth factor A (VEGF-A) interacting with the vascular endothelial growth factor
receptor 2 (VEGFR2) or the co-receptor neuropilin-1 (NRP-1). The Vegfa gene can be spliced in many ways, creating
numerous VEGF-A isoforms, each with unique interactions with VEGFR2. Several drugs have been approved as the
first- 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, as
a result, are less effective and have considerable adverse effects. As a natural drug, Paclitaxel has an anti-angiogenic
effect in addition to its chemotherapeutic effect. However, different doses of paclitaxel have different anti-angiogenic
mechanisms and different effects on different species.
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