Molecular facets and biochemical cross-talk of angiogenesis: Potential therapeutic targets

Abstract

Angiogenesis is a well conserved biological process for vascular growth and development. A canonical approach towards angiogenesis as provided insight in understanding the molecular and biochemical mechanism which differs in cancer angiogenesis. Vascular sprouting is a critical process in cancer metastasis and invasion, cancer cells release certain growth factors that can activate downstream signalling pathways to initiate VEGFR2 gene transcription further instigating angiogenesis via VEGFR2 receptors. Furthermore, paracrine signalling through these growth factor can directly bind to VEFGR2 causing its activation. There are several factors that has been procured by cancerous cells to sustain its survival. Over a period, studies have shown that there are various downstream signalling pathways taking part in cancer prognosis as most of the signalling pathways aim to inhibit endogenous VEGFR2 inhibitory molecules such as Thrombospondin. Cancer is a multifactorial disease and therefore hypoxia, changes in cellular pH, metabolic reprogramming, mutations in proto-oncogenes and tumour suppressor genes have been the contributory factors for cancer cell growth. Understanding the biochemical and molecular mechanism have paved its way in unsnarling the potential therapeutic targets. In addition, the role of adhesion molecules has also been studies they act as an adaptor molecule for an example αvβ6 in hippo pathway activates VEGFR for tip cell activity. Thereafter, focusing on these aspects of angiogenesis can provide several targets that would be used for developing and designing inhibitory antagonist, oncogene targeting drugs or anti-cancer drugs.