Angiogenesis inhibitors in the treatment of prostate cancer.
BACKGROUND
Prostate carcinoma is the most common non-cutaneous malignancy in U.S. men. The efficacy of docetaxel and prednisone in metastatic castrate-resistant prostate cancer (mCRPC) has been shown to improve overall survival; however, its effect is not durable, highlighting the need for new therapies.


METHODS
We will review the development of some of the leading compounds with direct and indirect antiangiogenic activity in prostate cancer including antibodies to VEGF and its receptors, small-molecule inhibitors of downstream signaling, immunomodulatory drugs with antiangiogenic activity, and compounds thought to directly inhibit or destroy vascular endothelial cells.


RESULTS
The reader will gain a basic understanding of the role of angiogenesis in prostate cancer growth and metastasis. Current and potential targets of angiogenesis and their corresponding drugs under development for prostate cancer are discussed.


CONCLUSIONS
There are now multiple early-phase clinical trials of antiangiogenic agents alone or in combination in prostate cancer. Several of these agents are now in Phase III development. Combined therapy with two antiangiogenic compounds may improve the activity of either compound alone. Multiple targets in the angiogenesis pathway continue to be elucidated and should remain an active area of investigation for the treatment of prostate cancer.
Kluetz
Paul G
PG
National Cancer Institute, Medical Oncology Branch, Building 10, Room 12N226, 9000 Rockville Pike Bethesda, MD 20892, USA.
Figg
William D
WD
Dahut
William L
WL
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D000077143:Docetaxel; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D011241:Prednisone / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000150:complications* / Q000188:drug therapy; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000008:administration & dosage; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D042442:Vascular Endothelial Growth Factors
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D043823:Taxoids; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000077143:Docetaxel; D011241:Prednisone