Language
English
Publication Date
10-28-2025
Journal
Biology
DOI
10.3390/biology14111510
PMID
41300302
PMCID
PMC12650002
PubMedCentral® Posted Date
10-28-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Sirtuin 1 (SIRT1), an NAD+-dependent histone deacetylase, exerts complex and context-dependent effects in breast and gynecological cancers. By deacetylating histone and non-histone proteins such as p53, FOXO, and NF-κB, SIRT1 regulates essential processes including DNA repair, apoptosis, metabolism, and stress response. In breast cancer, SIRT1 may act as a tumor suppressor in early stages by maintaining genomic stability but promotes epithelial–mesenchymal transition, metastasis, and chemoresistance in aggressive subtypes such as triple-negative breast cancer. Similarly, in gynecological cancers, SIRT1 displays dual roles: promoting proliferation via estrogen signaling and p53/FOXO1 inhibition in Type I endometrial cancer yet potentially supporting DNA repair in high-grade Type II tumors. Its overexpression in ovarian and cervical cancers is linked to enhanced survival and drug resistance. Preclinical studies show that pharmacological inhibition of SIRT1 (e.g., with EX-527 or cambinol) restores chemosensitivity and reduces tumor cell viability, suggesting potential for SIRT1 inhibitors as adjuncts in cancer therapy. However, clinical trials specifically targeting SIRT1 in these cancers remain limited. Further investigation is needed to define therapeutic windows, molecular contexts, and combination strategies that could optimize SIRT1-targeted therapies. This review summarizes the current understanding of SIRT1’s roles in breast and gynecologic malignancies.
Keywords
SIRT1, breast cancer, gynecologic malignancies, SIRT1 inhibitors, biomarker
Published Open-Access
yes
Recommended Citation
Jianmin Ding, Matthew T Ye, and Songlin Zhang, "The Roles of Sirt1 in Breast and Gynecologic Malignancies" (2025). Faculty, Staff and Students Publications. 7484.
https://digitalcommons.library.tmc.edu/baylor_docs/7484