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Effects of angiogenesis inhibitors on multistage carcinogenesis in mice

G Bergers1, K Javaherian, K M Lo

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

Science (New York, N.Y.)
|April 30, 1999
PubMed

Insights

Targeting angiogenesis inhibitors to specific cancer stages is key. Different anti-angiogenic drugs show varied efficacy in preventing tumor growth, intervening in expansion, or regressing established cancers.

Area of Science:

  • Oncology
  • Cancer Biology
  • Angiogenesis Research

Background:

  • Solid tumors require new blood vessel formation (angiogenesis) for growth and progression.
  • The RIP1-Tag2 transgenic mouse model exhibits an angiogenic switch in premalignant lesions, progressing to invasive carcinomas.
  • Understanding the role of angiogenesis is crucial for developing effective cancer therapies.

Purpose of the Study:

  • To evaluate the efficacy of four distinct angiogenesis inhibitors in a pancreatic cancer model.
  • To determine if the timing of anti-angiogenic drug administration impacts treatment outcomes.
  • To compare the effects of inhibitors at different stages of cancer development: premalignant lesions, small tumors, and large cancers.

Main Methods:

  • Utilized the RIP1-Tag2 transgenic mouse model of pancreatic islet cell carcinogenesis.
  • Administered four angiogenesis inhibitors: AGM-1470, angiostatin, BB-94, and endostatin.
  • Tested inhibitor efficacy across three distinct disease stages: prevention of angiogenic switch, intervention during tumor expansion, and regression of advanced cancers.

Main Results:

  • Each of the four angiogenesis inhibitors (AGM-1470, angiostatin, BB-94, endostatin) demonstrated unique efficacy profiles.
  • The effectiveness of the inhibitors varied significantly depending on the stage of cancer progression at which they were administered.
  • No single inhibitor was universally effective across all tested stages of tumor development.

Conclusions:

  • Anti-angiogenic therapies may be most effective when precisely targeted to specific stages of cancer progression.
  • The choice of angiogenesis inhibitor and its administration timing are critical factors for therapeutic success.
  • This study highlights the dynamic nature of tumor angiogenesis and its implications for drug development.

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