MAPK signaling mediates tamoxifen resistance in estrogen receptor-positive breast cancer - PubMed
8 days ago
- #MAPK signaling
- #Breast cancer
- #Tamoxifen resistance
- Tamoxifen resistance in ER-positive breast cancer is a significant clinical challenge, often not due to ER loss or mutation but changes in proliferative and survival pathways.
- MAPK signaling pathways regulate cell growth, proliferation, and apoptosis, playing a key role in tamoxifen resistance.
- Molecular factors like growth factors, RNA-binding proteins, non-genomic ER variants, and microRNAs promote survival of tamoxifen-resistant cells via MAPK signaling.
- Mitochondrial dynamics and MAPK-mediated phosphorylation of ERα contribute to resistance through adaptive mechanisms and ligand-independent activation.
- MAPK synergizes with pathways like PI3K/AKT and receptor tyrosine kinases (EGFR, IGF-1R, FGFR) to enhance signaling redundancy and compensatory survival mechanisms.
- Therapeutic interventions targeting MAPK, including small-molecule inhibitors and RNA-based therapies, show promise in overcoming tamoxifen resistance.