Association of retinoids, retinoic acid receptors and epigenetics in breast cancer - PubMed
9 hours ago
- #breast cancer
- #epigenetics
- #retinoic acid
- Retinoic acid signaling, mediated through RARs and RXRs, regulates cell differentiation, proliferation, and apoptosis.
- Therapeutic potential of retinoic acid in breast cancer is underexplored compared to hematologic malignancies.
- Epigenetic regulation, including promoter hypermethylation and histone deacetylation, silences RARβ2 and disrupts retinoic acid signaling.
- Luminal tumors with preserved RARα and CRABP2 expression show strong retinoic acid sensitivity.
- HER2-enriched and triple-negative breast cancers exhibit retinoid resistance due to MYC-driven CRABP2 suppression and DNA hypermethylation.
- Epigenetic therapies (DNMT or HDAC inhibitors) can restore RARβ2 expression and resensitize tumors.
- Combination regimens (e.g., retinoic acid with entinostat and doxorubicin) show antitumor synergy in preclinical models.
- Retinoic acid modulates the tumor microenvironment, affecting angiogenesis, fibroblast activation, and immune responses.
- Stromal RARβ signaling can paradoxically promote tumor progression.
- Future clinical development should focus on biomarker-driven stratification, pharmacological optimization, and combination therapies.
- Methylation-based classifiers may identify retinoid-responsive triple-negative breast cancer subsets.