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Targeting the Pro-survival Protein BCL-2 to Prevent Breast Cancer

Adelaide Young1, Wen Bu1, Weiyu Jiang1

  • 1Lester & Sue Smith Breast Center, Baylor College of Medicine, Houston, Texas.

Cancer Prevention Research (Philadelphia, Pa.)
|October 20, 2021
PubMed

Insights

New research shows prophylactic treatment with venetoclax, a BCL-2 inhibitor, effectively prevents PIK3CA-mutated breast cancer in mice. This offers a promising, safer alternative for breast cancer prevention strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Prevention

Background:

  • Current breast cancer chemoprevention involves long treatment durations and significant side effects.
  • Novel, safer, and shorter chemopreventive strategies are urgently needed.

Purpose of the Study:

  • To develop and validate a novel murine model for breast cancer initiation and chemoprevention studies.
  • To evaluate the efficacy of venetoclax, a BCL-2 inhibitor, as a prophylactic agent against PIK3CA-mutated breast cancer.

Main Methods:

  • Development of a murine model using lentivirus delivery of a common PIK3CA mutation to induce mammary atypia and ductal carcinomas.
  • Treatment of mice with atypia using venetoclax, a BH3 mimetic targeting BCL-2.
  • Assessment of tumor progression, overall survival, and pulmonary metastasis.

Main Results:

  • Venetoclax treatment significantly delayed tumor progression in the developed murine model.
  • Prophylactic venetoclax administration improved overall survival rates in mice.
  • A reduction in pulmonary metastasis was observed following venetoclax treatment.

Conclusions:

  • Prophylactic inhibition of the pro-survival protein BCL-2 using venetoclax is a viable strategy for preventing PIK3CA-mutated breast cancer.
  • This approach may offer a safer and shorter alternative to current breast cancer prevention regimens.
  • The developed murine model is effective for testing chemopreventive therapeutics.

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