Angiogenesis inhibitors in the treatment of colorectal cancer.
Angiogenesis is critical for normal and pathologic processes in new blood vessel formation. A recent significant advance in the treatment of metastatic colorectal cancer has occurred by the development of agents targeting key regulatory molecules involved in this process, specifically vascular endothelial growth factor (VEGF). These angiogenesis inhibitors, include bevacizumab (Avastin, Genentech, Inc, South San Francisco, CA), which binds free VEGF. Recently, a phase III, multicenter, double-blind, randomized, placebo-controlled trial was designed to determine whether or not the addition of bevacizumab to first-line irinotecan, 5-fluorouracil, and leucovorin chemotherapy was completed in patients with metastatic colorectal cancer. The trial showed a higher response rate, longer time to tumor progression, and prolonged overall survival in patients with metastatic colorectal cancer. Of note, this was the first large, randomized, phase III study to show the importance of targeting VEGF and tumor angiogenesis for the treatment of human cancer. Other potential targets of angiogenesis, such as the VEGF receptor and multi-targeted agents, are undergoing evaluation in clinical trials.
Iqbal
Syma
S
Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USA.
Lenz
Heinz-Josef
HJ
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000068258:Bevacizumab; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D006801:Humans; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors*
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042442:Vascular Endothelial Growth Factors; D000068258:Bevacizumab; D040262:Receptors, Vascular Endothelial Growth Factor