Farydak (panobinostat)

These subtypes exhibited distinct drug sensitivities (C1 sensitive to panobinostat, MK-2206, 17-AAG; C2 sensitive to venetoclax) and predicted immunotherapy responses (C1 potentially benefiting more from anti-PD-1)...Crucially, aberrant PKM2 overexpression was linked to imatinib (IM) resistance...To mitigate vMO toxicity, IL3-Lamp2b-engineered exosomes were developed, demonstrating efficient vMO loading, targeted delivery to leukemia cells, potent PKM splicing correction, significant IM resistance reversal, and minimal stromal cell toxicity. This work defines glycolysis-based AML subtypes with therapeutic implications and establishes engineered exosome-delivered vMO as a promising strategy to overcome drug resistance in hyper-glycolytic myeloid leukemia.

LRG also showed greater sensitivity to PD-1/CTLA4 inhibitors and chemotherapeutic agents (e.g., Panobinostat and Doxorubicin). This study reveals the molecular mechanisms and clinical significance of NCCGs in CC and epithelial-origin cancers. NCCGs hold value in molecular classification, prognostic assessment, and predicting therapeutic responses, offering new markers and targets for precision medicine.

Our study examined two "first-in-class" RNA Pol I inhibitors, CX-5461 and BMH-21, which differentially regulate NK cell-activating and inhibitory ligand expression in MM. This effect was modulated by Lenalidomide and Panobinostat. Moreover, RNA Pol I inhibition enhanced Daratumumab-mediated antibody-dependent cellular cytotoxicity (ADCC) of NK cells against MM, uncovering novel immuno-mediated antitumor mechanisms.

Panobinostat, Pirinixic acid, and Fluorouracil were predicted to be the potential BCL2L12-targeted drug for HCC. Our findings offer an understanding of the Oncogenic Role of BCL2L12 associated with immune status in the prognosis of HCC and provide potential strategies for currently limited treatment.

We therefore characterized the impact of pan-HDAC inhibitor, panobinostat, and class I HDAC inhibitor, nanatinostat, on the growth, survival, and lytic reactivation of four EBV-positive cell lines: P3HR1-ZHT BL, Jijoye BL, IBL-1 immunoblastic lymphoma, and de novo infection derived lymphoblastoid cell lines (LCL). Single-cell RNA sequencing provided evidence of upregulated immune signaling pathways in this abortive lytic population. This study provides in depth characterization of lytic reactivation with a biologically relevant stimulus.

P=N/A, N=10, Not yet recruiting, Shunyi Women's & Children's Hospital of Beijing Children's Hospital; Shunyi Women's & Children's Hospital of Beijing Children's Hospital

P=N/A, N=10, Not yet recruiting, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health; Beijing Children's Hospital, Capital Medical Universit

P=N/A, N=10, Recruiting, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health; Beijing Children's Hospital, Capital Medical Universit

Utilizing barcoded analysis in our recently developed ex vivo glioblastoma cerebral organoid (GLICO) model, we discerned distinct cell state sensitivities to the MES-L enhancing histone deacetylase inhibitor, panobinostat, which are contingent on the inducible modulation of the mesenchymal transcription factor FOSL1. The strategic combination of MES-L enhancing and MES-l suppressing genetic perturbations or drugs significantly increases anti-glioma activity in a strategy we call state-selective lethality. Overall, our findings highlight the critical role of cell state plasticity in the response of GSCs to anti-tumor therapeutic stress and underscore the potential for novel GBM combination drug strategies.

P4, N=356, Recruiting, Novartis Pharmaceuticals | Active, not recruiting --> Recruiting

Collectively, our studies established a previously unrecognized GATA2/GATA3-FOXA1-HER3 axis as a key regulatory network in BLBC progression. We provide strong experimental data supporting that the two HDACi, Romidepsin and Panobinostat may be repurposed as effective therapeutic agents for BLBC.

Importantly, combination of adagrasib with panobinostat demonstrated enhanced antitumor activity in vitro and in vivo. Overall, our data elucidate a novel mechanism of adagrasib, which will be critical for the clinical application of adagrasib.