Farydak (panobinostat)

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.

These findings reveal a novel cytoplasmic function of WEE1 in sustaining MYC stability and chemoresistance. Targeting WEE1 destabilizes MYC and enhances therapeutic response, supporting the combination of MK-1775 and Panobinostat as a promising treatment strategy for EAC.

In search of the molecular mechanism underlying a potentially intrinsic panobinostat resistance, we identified up-regulation of the HDAC8-transforming growth factor-β (TGFβ)-epithelial-to-mesenchymal transition (EMT) axis in the TO model, whereas subsequent HDAC8 depletion increased the sensitivity to panobinostat. These data highlight the utility of personalized drug screenings on TOs to identify suitable drug targets and inhibitors for more effective treatment of clinically aggressive meningiomas and to help advance our understanding of counteracting resistance mechanisms.

Our study identified IL3RA as novel biomarker and therapeutic target for ER+ breast cancer. Further validation and mechanistic studies are warranted to advance precision oncology strategies for ER+ breast cancer management.

P1/2, N=49, Active, not recruiting, Erasmus Medical Center | Recruiting --> Active, not recruiting

Viability, cytotoxicity, and caspase-3/7 activity were assessed following single-agent treatment with asciminib, ponatinib, bortezomib, or panobinostat. Co-inhibition of proteasomes and histone deacetylases eliminates TKI-refractory BCR::ABL1-driven leukaemia cells by inducing mitochondrial apoptosis and loss of clonogenic potential. These findings indicate a clinically actionable, TKI-independent strategy for the salvage treatment of multidrug-resistant CML.

Furthermore, panobinostat downregulated a network of oncogenes and cell cycle regulators, including c-Myc and key cyclins. These findings indicate that panobinostat can enhance 5-FU cytotoxicity by targeting TS expression and reprogramming oncogenic transcriptional networks, supporting its potential as a complementary strategy for overcoming fluoropyrimidine resistance in GC therapy.

This finding highlights the functional relevance of IMiD's inherent polypharmacology in circumventing primary resistance mechanisms at the cellular level. Together, our results identify the ARID2-containing PBAF complex as a critical vulnerability in resistant myeloma cells and provide a mechanistic rationale for designing combination strategies that co-target this complex, with the potential to enhance therapeutic efficacy by overcoming drug resistance.

Pharmacologic inhibition of HDAC1 with panobinostat recapitulated the tumor-suppressive effects observed with MIG-6 overexpression. These findings suggest that HDAC1 may represent a potential therapeutic target in EEC and that HDAC inhibition can attenuate early tumor progression and angiogenic signaling in preclinical models. Implications: This study identifies the MIG-6/HDAC1 axis as a key regulator of angiogenesis in EEC, highlighting HDAC1 inhibition as a promising targeted therapeutic strategy for early tumor suppression.

Moreover, with the co-delivery of siSTAT3, the exosomes display various functionalities, such as inhibiting GB proliferation and invasion, preventing astrocyte reactivity, and reducing M2 macrophage infiltration. This "one-two punch" approach offers a powerful combined anticancer effect through simultaneously targeting tumor cells and reshaping the tumor microenvironment, which holds considerable promise in curbing GB recurrence and provides hope for more effective future treatments.