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.
Ma
Wen W
WW
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231-1000, USA. wma2@jhmi.edu
Jimeno
Antonio
A
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D016503:Drug Delivery Systems; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D016337:RNA, Catalytic / Q000494:pharmacology / Q000627:therapeutic use; D040262:Receptors, Vascular Endothelial Growth Factor / Q000187:drug effects; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects
D020533:Angiogenesis Inhibitors; C121301:Angiozyme; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016337:RNA, Catalytic; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; D013792:Thalidomide; D011505:Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor