Effects of angiogenesis inhibitors on multistage carcinogenesis in mice.
Solid tumors depend on angiogenesis for their growth. In a transgenic mouse model of pancreatic islet cell carcinogenesis (RIP1-Tag2), an angiogenic switch occurs in premalignant lesions, and angiogenesis persists during progression to expansive solid tumors and invasive carcinomas. RIP1-Tag2 mice were treated so as to compare the effects of four angiogenesis inhibitors at three distinct stages of disease progression. AGM-1470, angiostatin, BB-94, and endostatin each produced distinct efficacy profiles in trials aimed at preventing the angiogenic switch in premalignant lesions, intervening in the rapid expansion of small tumors, or inducing the regression of large end-stage cancers. Thus, anti-angiogenic drugs may prove most efficacious when they are targeted to specific stages of cancer.
Bergers
G
G
Department of Biochemistry and Biophysics and Hormone Research Institute, University of California, San Francisco, 513 Parnassus Ave, San Francisco, CA 94143-0534, USA.
Javaherian
K
K
Lo
K M
KM
Folkman
J
J
Hanahan
D
D
D043168:Angiostatins; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D018273:Carcinoma, Islet Cell / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D003094:Collagen / Q000494:pharmacology; D003510:Cyclohexanes; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D043169:Endostatins; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D010446:Peptide Fragments / Q000494:pharmacology; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000494:pharmacology; D010958:Plasminogen / Q000494:pharmacology; D012717:Sesquiterpenes / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D003510:Cyclohexanes; D043169:Endostatins; D010446:Peptide Fragments; D012717:Sesquiterpenes; D013876:Thiophenes; D010649:Phenylalanine; D043168:Angiostatins; D010958:Plasminogen; D003094:Collagen; C080985:batimastat; D000077609:O-(Chloroacetylcarbamoyl)fumagillol