Farydak (panobinostat)

Using a focused epigenetic compound screen across multiple MRT cell lines, we identified that the HDAC inhibitor panobinostat (LBH589) and the BET inhibitor birabresib (OTX015) act synergistically to inhibit cell proliferation, with combination index (CI) values consistently <1. In vivo, this dual-epigenetic targeting significantly attenuated tumor growth in MRT xenograft models, outperforming either monotherapy, and was associated with suppressed proliferation and E2F1 signaling. Our findings unveil a novel synergistic strategy that pharmacologically recapitulates a core SMARCB1-mediated tumor-suppressive circuit, nominating combined HDAC and BET inhibition as a promising therapeutic avenue for MRT.

In conclusion, we identified molecular subtypes of NPC, constructed preliminary diagnostic and prognostic marker panels, and observed the therapeutic potential of Panobinostat, as a monotherapy and in combination with radiotherapy. These findings provide a solid foundation for precision diagnosis, prognostic stratification, and personalized treatment strategies for NPC.

P4, N=296, Recruiting, Novartis Pharmaceuticals | Active, not recruiting --> Recruiting | Trial completion date: Sep 2027 --> Apr 2032

Anti-glioma effects with the lowest drug concentrations were achieved for proteasome inhibitors (carfilzomib, bortezomib, ixazomib), and HDAC inhibitors (panobinostat, romidepsin). The impact of their drug targets PSMB5 and HDAC1/2 on the growth of GBM cells was successfully validated by RNAi experiments. We established an aHTS platform for GBM TOs, and identified proteasome and HDAC inhibitors as promising drugs for the treatment of GBMs.

This study integrated multi-omics data with machine learning to develop a robust four-gene diagnostic model for NPC. The core genes (COL4A2, LAMB1, ACTA2, CCL2) are associated with tumor progression, prognosis, immune regulation, and distinct biological pathways. Our findings provide a valuable tool for the diagnosis and risk stratification of NPC and reveal potential therapeutic targets worthy of further investigation.

To nominate therapeutic targets across subtypes, we developed a multiomic machine-learning approach and validated MTA1 as a contributor to panobinostat resistance. Altogether our findings underscore the complex nature of AML and provide a clinically and translationally informed unified view that reveals coalescent phenotypes across multiomic layers.

Samples with low stemness and elevated pyroptosis showed enhanced inferred drug resistance, particularly to LBH589...CONCLUSION‌: This study highlights the molecular heterogeneity of gastric cancer, demonstrating how distinct cell death patterns and PTM features shape prognosis and drug sensitivity. The identified biomarkers and resistance profiles may provide valuable guidance for personalized therapeutic strategies.

Our study demonstrates that LBH589 not only directly induces apoptosis, inhibits proliferation, migration, and invasion, but also enhances the anti-tumor immune response through improving tumor immunogenicity. These findings not only broaden the mechanistic understanding of HDACi in TNBC, but also provide a theoretical basis for combining epigenetic therapy with immunotherapy, supporting LBH589 as a potential immunotherapy sensitizer for triple-negative breast cancer.

Decreased expression of stemness-related genes upon KDMi treatment in FaDu cells was associated with decreased binding of KDM4A and/or KDM6B at SOX2 and POU5F1 gene promoters. The suppression of stemness-associated phenotype, and the concurrent promotion of apoptosis by the studied combinations of chemicals, suggest their potential as a novel therapeutic strategy in HNSCC.

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). Functional validation through a Cas9-RNP approach revealed that the CD137 receptor is indeed involved in preventing successful lytic reactivation. These data have important implications for how we approach oncolytic therapies for EBV-associated malignancies.

Ve combined with Pa exerts a synergistic inhibitory effect on the growth and metastasis of FRO and ARO cells, while promoting apoptosis and cellular redifferentiation. This combination may provide a potential therapeutic strategy for ATC.

Importantly, combined treatment with panobinostat and the anti-angiogenic agent anlotinib resulted in superior inhibition of tumor growth and vascularization compared with either monotherapy in patient-derived organoid xenograft models. Together, these findings uncover an enzymatic activity-independent RNA regulatory function of NQO1 in ESCC and provide a mechanistic rationale for targeting the NQO1/AGRN axis.