Effects of Angiogenesis Inhibitors on Multistage Carcinogenesis in Mice

Author:

Bergers Gabriele1,Javaherian Kashi2,Lo Kin-Ming3,Folkman Judah2,Hanahan Douglas1

Affiliation:

1. Department of Biochemistry and Biophysics and Hormone Research Institute, University of California, San Francisco, 513 Parnassus Ave, San Francisco, CA 94143–0534, USA.

2. Department of Surgery, Children's Hospital Medical Center and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.

3. Lexigen Pharmaceuticals, 125 Hartwell Avenue, Lexington, MA 02173, USA.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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