Strategies for suppressing angiogenesis in gynecological cancers.

Angiogenesis is vital for numerous physiological and pathological processes, including proliferation, invasion and metastasis in malignancies. Various strategies to suppress angiogenesis are under evaluation in gynecological malignancies, and ovarian cancer--the deadliest of them--has been the focus. Interruption of interaction between vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) with a monoclonal antibody, bevacizumab, has so far been the most promising antiangiogenic strategy in ovarian cancer clinically but is overshadowed by higher than expected frequency of severe toxicities. Interception of VEGF with receptor decoys, such as VEGF-Trap, and inhibiting receptor tyrosine kinases for VEGF and related growth factors with small molecule inhibitors have shown encouraging results in early phase trials of ovarian cancer; validation is ongoing in larger studies. Another approach is targeting pre-mRNA for VEGF receptors with ribozyme (angiozyme). The knowledge gained from developing these different classes of antiangiogenic agents will lay the path to future trials of other types of gynecological cancers.