Genome-wide CRISPR/Cas9 screen identified MCL1 as a senolytic target for clearing palbociclib-induced senescent and PD-L1-positive cells in colorectal cancer - PubMed
3 hours ago
- #Senolysis
- #MCL1
- #Colorectal Cancer
- Palbociclib induces senescence in colorectal cancer cells, leading to drug resistance, anti-apoptosis, PD-L1 upregulation, and CD8+ T cell inhibition.
- CRISPR/Cas9 screening identified MCL1 as a key senolytic target to eliminate palbociclib-induced senescent cells.
- Senescent cells upregulate ZHX2 and MCL1, enhancing resistance to apoptosis and T cell cytotoxicity.
- Combining palbociclib with an MCL1 inhibitor activates apoptotic pathways, effectively killing senescent cells.
- A proposed seno-therapy (palbociclib pretreatment plus combination with MCL1 inhibitor) reduces tumor growth, improves survival, and enhances T cell function in mouse models.