Paradigm Shift in the Therapeutic Potential of Endogenous Angiogenesis Inhibitors for Cancer Therapy: Historical Perspective and Future Direction
Pp. 320-362 (43)
Mohanraj Dhanabal and Natarajan Sethuraman
Angiogenesis, the formation of new blood vessels from preexisting
microvasculature is a highly regulated process. Angiogenesis is controlled by both positive
and negative factors thus providing several targets for drug discovery. Targeting tumor
endothelial cells has gained much attention with the notion that tumors can be starved to
death by cutting the lifeline of tumor cells, i.e. vascular endothelial cells. In this regard, the
inhibition of angiogenesis represents a new approach to cancer therapy and several agents
and approaches are in different stages of clinical development. A paradigm shift is expected
in the treatment of malignancies because of the recent introduction of mechanism-based
systemic therapies that may be more specific, less toxic, and more effective. These
inhibitors were recently shown to constitute a new modality for cancer treatment. In this
chapter, we will review the recent angiogenesis inhibitors-related patent literature. This
review will cover specifically the discovery and development disclosures of endogenous
inhibitors. The scope of this chapter is to give the reader a well structured patent literature
overview of agents targeting different steps of the angiogenic process. Finally, we have
summarized the key attributes of the emerging endogenous angiogenesis inhibitors that
make them a potent antitumor agents.
Angiogenesis, angiostatin, anti-angiogenesis inhibitors, cancer,
endostatin, receptor tyrosine kinase and kringle, vascular target, VEGF.
EMD Serono Research Institute Inc., 45A Middlesex Turnpike, Billerica, MA 01821, USA.