Future directions with angiogenesis inhibitors in colorectal cancer.
The recent US Food and Drug Administration's approval of bevacizumab has reinvigorated antiangiogenic research and has moved colorectal cancer to the forefront of study for the most promising drug candidates in this class. Predicting future directions in this field requires a return to the challenges of the past. Antiangiogenic drugs have necessitated new study design paradigms and imaging techniques in the assessment of drug activity and in dose selection. The success of bevacizumab and the promise of vatalanib (PTK787/ZK222584) and the cyclooxygenase-2 inhibitors also illustrate the importance of these adaptations. A better understanding of the determinants of response to antiangiogenic agents and their mechanisms of action, especially in combination with cytotoxic drugs, is crucial to future drug development.
University of Pennsylvania Cancer Center, 3400 Spruce St, Philadelphia, PA 19104, USA.
Joshua H
JH
Bilenker
Daniel G
DG
Haller
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002986:Clinical Trials as Topic; D017321:Clinical Trials, Phase I as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004195:Disease Models, Animal; D017277:Drug Approval; D005544:Forecasting; D006801:Humans; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010793:Phthalazines / Q000008:administration & dosage; D011379:Prognosis; D011725:Pyridines / Q000008:administration & dosage; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D014481:United States; D014486:United States Food and Drug Administration
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D010793:Phthalazines; D011725:Pyridines; D000068258:Bevacizumab; C404768:vatalanib