Targeting the Pro-survival Protein BCL-2 to Prevent Breast Cancer.
Cancer Prev Res (Phila)
; 15(1): 3-10, 2022 01.
Article
in En
| MEDLINE
| ID: mdl-34667127
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Cancer Prev Res (Phila)
Journal subject:
NEOPLASIAS
Year:
2022
Document type:
Article