Targeting angiogenesis in cancer treatments: where do we stand?
Date
2016
Authors
Petrovic, N.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Pharmacy and Pharmaceutical Sciences, 2016; 19(2):226-236
Statement of Responsibility
Conference Name
DOI
Abstract
Since early seventies of the twentieth century, through seminal work of Judah Folkman, angiogenesis, the process of new blood vessel sprouting from the existing vasculature, was recognized as a necessary part of wound healing, development of placenta, tissue growth and regeneration as well as cancer progression. This process is induced by low tissue oxygenation and it is a crucial prerequisite for rapid tissue growth, providing proper oxygen supply and removal of toxic metabolites. Suppression of angiogenesis as a way of slowing down tumor progression continues to be one of the most important areas of cancer research.
The angiogenic process is relatively complex and it is regulated by numerous pro- and anti-angiogenic factors. Intensive research in the last twenty years resulted in identification of more than 300 angiogenesis inhibitors, a trend that is expected to continue. Unfortunately, most of these treatments have demonstrated unacceptable toxicities or failed to show activity in clinical studies. Although not yet completely understood, the complex process of tumor angiogenesis involves highly regulated orchestration of multiple activating and inhibiting factors. Vascular endothelial growth factor (VEGF) and its cognate receptors appear to play a central role in angiogenesis activation.
Thus, initial efforts to develop anti-angiogenic treatments focused largely on inhibiting VEGF action. Such approaches, however, often lead to transient responses due to multiple pathways able to compensate for a single pathway inhibited. Accordingly, more recent treatments have focused on simultaneous inhibition of multiple signaling pathways. This review concentrates on identifying those anti-angiogenic treatments that made to the clinic by receiving approval by USA Food and Drug Administration (FDA) as treatments for cancer. Regardless of observed problems, it is an imperative that research in angiogenesis regulation continues. Consequently, pharmacological manipulation of angiogenesis may yet to introduce truly new pharmacological therapies into the field of cancer therapy, the field that was rather dormant in the last several decades
School/Discipline
Dissertation Note
Provenance
Description
Access Status
Rights
Copyright 2016 the authors