Angiogenesis is the fundamental process by which new blood vessels are formed. Extensive research has shown that this event can be co-opted by
tumors to ensure their growth, survival and
metastasis. The study of
tumor angiogenesis therefore represents a promising area of research for development of anti-
cancer therapeutics.
Integrins, a family of cell surface molecules, are a major target of interest as they are known to play a vital role in
pathological angiogenesis. Remarkably, small
disulfide-rich
peptides known as
disintegrins, isolated from the
venoms of various snake species have been found to bind
integrins with extremely high affinity and block their function.
Disintegrins are capable of inhibiting several aspects of
tumor cell behavior both in vitro and in vivo, including adhesion, migration, invasion,
metastasis and angiogenesis. In this review, we will briefly discuss
tumor angiogenesis and molecules implicated in the angiogenic process, with a special focus on the role of
integrins. We will also discuss therapeutic approaches towards the treatment of
tumor angiogenesis, including non-
integrin-targeted agents currently in clinical trials. We will summarize the major findings from studies using
disintegrins to target
integrin-associated angiogenesis in
cancer models. Finally, we will present results obtained in our laboratory using the novel dimeric
disintegrin,
contortrostatin (CN), in studies of endothelial cells and models of breast, ovarian and
prostate cancer. In summary,
disintegrins represent an exciting new class of molecules that can potentially be used in a clinical setting to inhibit angiogenesis and augment conventional chemotherapeutic agents in the treatment of
cancer.