Language
English
Publication Date
1-1-2022
Journal
Cancer Prevention Research
DOI
10.1158/1940-6207.CAPR-21-0031
PMID
34667127
PMCID
PMC8741732
PubMedCentral® Posted Date
7-1-2022
PubMedCentral® Full Text Version
Author MSS
Abstract
Current chemopreventive strategies require 3-5 years of continuous treatment and have the concerns of significant side effects; therefore, new chemopreventive agents that require shorter and safer treatments are urgently needed. In this study, we developed a new murine model of breast cancer that mimics human breast cancer initiation and is ideal for testing the efficacy of chemopreventive therapeutics. In this model, introduction of lentivirus carrying a PIK3CA gene mutant commonly found in breast cancers infects a small number of the mammary cells, leading to atypia first and then to ductal carcinomas that are positive for both estrogen receptor and progesterone receptor. Venetoclax is a BH3 mimetic that blocks the anti-apoptotic protein BCL-2 and has efficacy in treating breast cancer. We found that venetoclax treatment of atypia-bearing mice delayed the progression to tumors, improved overall survival, and reduced pulmonary metastasis. Therefore, prophylactic treatment to inhibit the pro-survival protein BCL-2 may provide an alternative to the currently available regimens in breast cancer prevention. PREVENTION RELEVANCE: This study demonstrates that prophylactic treatment with the BCL2-specific antagonist venetoclax prevents breast cancer initiated by a mutated and activated PIK3CA, the most common breast oncogene.
Keywords
Animals, Apoptosis, Apoptosis Regulatory Proteins, Breast Neoplasms, Female, Humans, Mice, Proto-Oncogene Proteins c-bcl-2, Receptors, Estrogen, breast cancer, chemoprevention, mouse model, PIK3CA, venetoclax
Published Open-Access
yes
Recommended Citation
Young, Adelaide; Bu, Wen; Jiang, Weiyu; et al., "Targeting the Pro-survival Protein BCL-2 to Prevent Breast Cancer" (2022). Faculty and Staff Publications. 2011.
https://digitalcommons.library.tmc.edu/baylor_docs/2011
Included in
Biological Phenomena, Cell Phenomena, and Immunity Commons, Life Sciences Commons, Medical Cell Biology Commons, Medical Microbiology Commons, Medical Molecular Biology Commons, Neoplasms Commons, Obstetrics and Gynecology Commons, Oncology Commons