Combination of HDAC inhibitor and PI3K inhibitor suppresses autophagy and induces apoptosis via cytoplasmic IκBα stabilization in p53-mutant diffuse large B-cell lymphoma
This study reveals that a dual inhibition strategy targeting HDAC and PI3K reduces tumor burden in p53-mutant DLBCL, suggesting a novel therapeutic approach.
Key Points
The combination of chidamide and duvelisib robustly induces apoptosis in p53-mutant DLBCL models.
Treatment with these inhibitors resulted in reduced tumor burden in xenograft mouse models, improving overall survival.
Mechanistically, the combination stabilizes IκBα and suppresses NF-κB activity, leading to inhibited autophagy and enhanced apoptosis.
This synergistic approach offers a promising therapeutic strategy for patients with treatment-refractory p53-mutant DLBCL.