^
    23d
    Approaches for prevention of tumors in patients with rhabdoid tumor predisposition syndrome. (PubMed, Neurooncol Adv)
    Potential maintenance regimens may include low-dose traditional chemotherapy or different epigenetic therapies designed to target the epigenetic imbalance that drives RTs. We here review several potential maintenance regimens that may be useful in RTPS.
    Review • Journal
    |
    SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1)
    |
    Tazverik (tazemetostat) • Farydak (panobinostat)
    23d
    Development of a prognostic model related to homologous recombination deficiency in glioma based on multiple machine learning. (PubMed, Front Immunol)
    Molecular docking highlighted several compounds, notably Panobinostat, as promising for high-risk patients. The prognostic model based on the HRD score threshold and associated genes in glioma offers new insights into the genomic and immunological landscapes, potentially guiding therapeutic strategies. The differential immune profiles associated with HRD-risk groups could inform immunotherapeutic interventions, with our findings paving the way for personalized medicine in glioma treatment.
    Journal • IO biomarker • Machine learning
    |
    HRD (Homologous Recombination Deficiency)
    |
    HRD • High HRD score
    |
    Farydak (panobinostat)
    24d
    MEF2C is a Potential Prognostic Biomarker and is Correlated with Immune Infiltrates in Lung Adenocarcinoma. (PubMed, Curr Med Chem)
    The results imply that MEF2C could be a valuable indicator for predicting outcomes and a possible target for immunotherapy for LUAD patients.
    Journal • Tumor mutational burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • MEF2C (Myocyte Enhancer Factor 2C)
    |
    Tasigna (nilotinib) • irinotecan • topotecan • Farydak (panobinostat)
    2ms
    Activating mutations remodel the chromatin accessibility landscape to drive distinct regulatory networks in KMT2A-rearranged acute leukemia. (PubMed, Hemasphere)
    Human KMT2A-r AML cells could be pharmacologically sensitized to NKG2D-CAR T cells by treatment with the histone deacetylase inhibitor LBH589 (panobinostat) which caused upregulation of NKG2D-ligand levels...Finally, the results were validated and extended to acute leukemia in infancy. Combined, activating mutations induced mutation-specific changes in the epigenetic landscape, leading to changes in transcriptional programs orchestrated by specific transcription factor networks.
    Journal
    |
    FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • RUNX1 (RUNX Family Transcription Factor 1) • KMT2A (Lysine Methyltransferase 2A) • STAT5B (Signal Transducer And Activator Of Transcription 5B) • MLLT3 (MLLT3 Super Elongation Complex Subunit) • STAT5A (Signal Transducer And Activator Of Transcription 5A) • NKG2D (killer cell lectin like receptor K1)
    |
    RAS mutation • KMT2A rearrangement • MLL rearrangement • NRAS G12D • NRAS G12 • FLT3 N676K • MLL mutation • KMT2A expression
    |
    Farydak (panobinostat)
    2ms
    Combination treatment with histone deacetylase and carbonic anhydrase 9 inhibitors shows therapeutic potential in experimental diffuse intrinsic pontine glioma. (PubMed, Brain Tumor Pathol)
    A synergy screen was conducted using CA9 inhibitor SLC-0111 and HDAC inhibitors panobinostat, vorinostat, entinostat, and pyroxamide. Additionally, the combination therapy induced a greater reduction in intracellular pH than either agent alone. Data from this study suggest that the combination of SLC-0111 and pyroxamide holds promise for treating experimental DIPG, and further investigation of this combination therapy in preclinical models is warranted to evaluate its potential as a viable treatment for DIPG.
    Journal • Epigenetic controller
    |
    CA9 (Carbonic anhydrase 9)
    |
    Zolinza (vorinostat) • Farydak (panobinostat) • Jingzhuda (entinostat) • SLC-0111
    2ms
    CINC424A2X01B Rollover Protocol (clinicaltrials.gov)
    P4, N=279, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    Jakafi (ruxolitinib) • Farydak (panobinostat)
    2ms
    Synergistic Cytotoxicity of Histone Deacetylase and Poly-ADP Ribose Polymerase Inhibitors and Decitabine in Breast and Ovarian Cancer Cells: Implications for Novel Therapeutic Combinations. (PubMed, Int J Mol Sci)
    We explored the synergistic cytotoxicity of histone deacetylase inhibitors (HDACis), poly(ADP-ribose) polymerase inhibitors (PARPis), and decitabine in breast (MDA-MB-231 and MCF-7) and ovarian (HEY-T30 and SKOV-3) cancer cell lines that were exposed to HDACi (panobinostat or vorinostat), PARPi (talazoparib or olaparib), decitabine, or their combinations. These results indicate that HDACi, PARPi, and decitabine combinations should be further explored in these tumor types. Further clinical validation is warranted to assess their safety and efficacy.
    Journal • PARP Biomarker • Epigenetic controller
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CASP3 (Caspase 3) • ANXA5 (Annexin A5)
    |
    Lynparza (olaparib) • Talzenna (talazoparib) • decitabine • Zolinza (vorinostat) • Farydak (panobinostat)
    2ms
    Phosphatase LHPP confers prostate cancer ferroptosis activation by modulating the AKT-SKP2-ACSL4 pathway. (PubMed, Cell Death Dis)
    Moreover, our findings reveal that Panobinostat, a potent histone-deacetylase inhibitor, intricately regulates LHPP expression at multiple levels through the inhibition of HDAC3. This complex modulation enhances the ferroptosis pathway, offering a novel mechanism for curtailing the growth of prostate tumors and highlighting its significant translational potential for clinical application.
    Journal
    |
    ACSL4 (Acyl-CoA Synthetase Long Chain Family Member 4) • HDAC3 (Histone Deacetylase 3) • SKP2 (S-phase kinase-associated protein 2)
    |
    Farydak (panobinostat)
    3ms
    Anti-tumour activity of Panobinostat in oesophageal adenocarcinoma and squamous cell carcinoma cell lines. (PubMed, Clin Epigenetics)
    Panobinostat exposure effectively impaired malignant features of oesophageal cancer cells. Because HDAC3 was shown to be overexpressed in oesophageal tumour samples, this epigenetic drug may represent an alternative therapeutic option for oesophageal cancer patients.
    Preclinical • Journal
    |
    HDAC2 (Histone deacetylase 2) • HDAC1 (Histone Deacetylase 1) • HDAC3 (Histone Deacetylase 3)
    |
    Farydak (panobinostat)
    4ms
    Investigation of SPOCD1 as A Suitable Diagnostic and Prognostic Biomarker in Various Common Cancer Types: Bioinformatics and Practical Analysis. (PubMed, Cell J)
    This study confirms the potential of SPOCD1 as a diagnostic and prognostic biomarker in prevalent cancers. However, extensive clinical data, particularly for CRC, are required to validate its reliability. Different COAD subtypes may exhibit varying correlations with SPOCD1 expression levels, underscoring the need for further investigation to fully understand its diagnostic and prognostic value.
    Journal
    |
    SPOCD1 (SPOC Domain Containing 1)
    |
    mirdametinib (PD-0325901) • Farydak (panobinostat)
    4ms
    Inhibition of glutaminolysis alone and in combination with HDAC inhibitor has anti-myeloma therapeutic effects. (PubMed, Cancer Drug Resist)
    Combining panobinostat with CB-839 resulted in enhanced cytotoxicity and increased caspase 3/7 activity. Glutaminolysis contributes to the viability of MM cells, and the GLS inhibitor CB-839 has been proven to be an effective treatment for enhancing the cytotoxic effect of HDAC inhibition. These results are clinically relevant and suggest that CB-839 is a potential therapeutic candidate for patients with MM.
    Journal • Combination therapy
    |
    CASP3 (Caspase 3) • CASP7 (Caspase 7) • GLS1 (Glutaminase)
    |
    Farydak (panobinostat) • telaglenastat (CB-839)
    4ms
    Investigating the impact of SMAD2 and SMAD4 downregulation in colorectal cancer and their correlation with immune markers, prognosis, and drug resistance and sensitivity. (PubMed, Mol Biol Rep)
    Reduced expression of SMAD2 and SMAD4 may be pivotal in CRC progression, impacting downstream genes unrelated to patient OS. These findings suggest a potential role for SMAD2 and SMAD4 as predictive markers for drug response in CRC patients.
    Journal
    |
    CD8 (cluster of differentiation 8) • SMAD4 (SMAD family member 4) • TGFB1 (Transforming Growth Factor Beta 1) • SMAD2 (SMAD Family Member 2)
    |
    Tasigna (nilotinib) • Farydak (panobinostat)
    4ms
    Targeting N4-acetylcytidine suppresses hepatocellular carcinoma progression by repressing eEF2-mediated HMGB2 mRNA translation. (PubMed, Cancer Commun (Lond))
    Our study identified a novel oncogenic epi-transcriptome axis involving NAT10-ac4C/eEF2-HMGB2, which plays a pivotal role in regulating HCC growth and metastasis. The drug Panobinostat validates the therapeutic potential of targeting this axis for HCC treatment.
    Journal
    |
    HMGB2 (High Mobility Group Box 2)
    |
    Farydak (panobinostat)
    4ms
    Identifying drug candidates for pancreatic ductal adenocarcinoma based on integrative multiomics analysis. (PubMed, J Gastrointest Oncol)
    The five drugs, including topotecan, PD-0325901, panobinostat, paclitaxel and 17-AAG, with the highest activity among 27 PDAC cell lines were filtered. Overall, the diagnostic model built based on four significant DMRs could accurately distinguish tumor and normal tissues. The five drug candidates might be repurposed as promising therapeutics for particular PDAC patients.
    Journal
    |
    FXYD3 (FXYD Domain Containing Ion Transport Regulator 3) • PRKCB (Protein Kinase C Beta)
    |
    paclitaxel • mirdametinib (PD-0325901) • topotecan • Farydak (panobinostat)
    5ms
    Comprehensive analysis of microRNAs modulated by histone deacetylase inhibitors identifies microRNA-7-5p with anti-myeloma effect. (PubMed, Int J Hematol)
    Transfection of myeloma cell lines with miR-7 suppressed cell proliferation, induced apoptosis, and enhanced the effects of the HDAC inhibitor panobinostat. Expression of miR-7 was downregulated by c-Myc inhibition, but upregulated by bortezomib...This miR-7 downregulation may be involved in HDAC inhibitor resistance. In addition, combinations of anti-myeloma drugs that complement changes in miRNA expression should be considered.
    Journal • Epigenetic controller
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MIR7 (MicroRNA 7)
    |
    bortezomib • Farydak (panobinostat)
    5ms
    CREB1 promotes expression of immune checkpoint HLA-E leading to immune escape in multiple myeloma. (PubMed, Leukemia)
    We discovered that HLA-E is regulated by cAMP responsive element binding protein 1 (CREB1) transcription factor by direct promoter binding; genomic and pharmacological inhibition of CREB1 reduced HLA-E levels even in the presence of IFN-γ or IFN-γ activating agents, such as immunomodulatory drugs and panobinostat...Treatment with a CREB1 inhibitor was able to restore NK cell-mediated cytotoxicity against MM cell lines and patient samples. In conclusion, our results strongly demonstrate that CREB1 inhibition promotes anti-tumoral immunity in MM by limiting HLA-E expression and enhancing the activity of NK cells.
    Journal
    |
    IFNG (Interferon, gamma) • NCAM1 (Neural cell adhesion molecule 1) • HLA-E (Major Histocompatibility Complex, Class I, E) • CREB1 (CAMP Responsive Element Binding Protein 1) • KLRC1 (Killer Cell Lectin Like Receptor C1)
    |
    Farydak (panobinostat)
    5ms
    Cubosomes functionalized with antibodies as a potential strategy for the treatment of HER2-positive breast cancer. (PubMed, J Colloid Interface Sci)
    Our research led to the design of immunocubosomes loaded with panobinostat and functionalized with trastuzumab antibodies, enabling precise targeting of breast cancer cells that overexpress HER2. Additionally, we found that panobinostat-loaded immunocubosomes were more cytotoxic, and in an uptake-dependant manner, towards a HER2-positive breast cancer cell line (SKBR3) compared to a cell line representing healthy cells (L929). These results support that the functionalization of cubosomes with antibodies enhances both the effectiveness of the loaded drug and its selectivity for targeting HER2-positive breast cancer cells.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    Herceptin (trastuzumab) • Farydak (panobinostat)
    5ms
    Panobinostat, Gemcitabine Hydrochloride, Busulfan, and Melphalan Before Stem Cell Transplant in Treating Patients With Refractory or Relapsed Multiple Myeloma (clinicaltrials.gov)
    P2, N=83, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Aug 2025 --> Jun 2024 | Trial primary completion date: Aug 2025 --> Jun 2024
    Trial completion • Trial completion date • Trial primary completion date
    |
    gemcitabine • Farydak (panobinostat) • melphalan • busulfan
    5ms
    Synergistic cytotoxicity of histone deacetylase and poly-ADP ribose polymerase inhibitors and decitabine in pancreatic cancer cells: Implications for novel therapy. (PubMed, Oncotarget)
    The combination of HDACi (panobinostat or vorinostat) with PARPi (talazoparib or olaparib) resulted in synergistic cytotoxicity in all cell lines tested. The 3-drug combinations also altered the epigenetic regulation of gene expression (NuRD complex subunits, reduced levels). This is the first study to demonstrate synergistic interactions between the aforementioned agents in pancreatic cancer cell lines and provides preclinical data to design individualized therapeutic approaches with the potential to improve pancreatic cancer treatment outcomes.
    Journal • BRCA Biomarker • PARP Biomarker • Epigenetic controller
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATRX (ATRX Chromatin Remodeler) • CASP3 (Caspase 3)
    |
    Lynparza (olaparib) • Talzenna (talazoparib) • decitabine • Zolinza (vorinostat) • Farydak (panobinostat)
    6ms
    TORSEL, a 4EBP1-based mTORC1 live-cell sensor, reveals nutrient-sensing targeting by histone deacetylase inhibitors. (PubMed, Cell Biosci)
    TORSEL is a unique living cell sensor that efficiently detects the inhibition of mTORC1 activity, and histone deacetylase inhibitors such as panobinostat target mTORC1 signaling through amino acid sensing.
    Journal • Epigenetic controller
    |
    EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)
    |
    sirolimus • Farydak (panobinostat)
    6ms
    Panobinostat, Gemcitabine Hydrochloride, Busulfan, and Melphalan Before Stem Cell Transplant in Treating Patients With Refractory or Relapsed Multiple Myeloma (clinicaltrials.gov)
    P2, N=83, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Aug 2024 --> Aug 2025 | Trial primary completion date: Aug 2024 --> Aug 2025
    Trial completion date • Trial primary completion date
    |
    gemcitabine • Farydak (panobinostat) • melphalan • busulfan
    7ms
    PBTC-047: Trial of Panobinostat in Children With Diffuse Intrinsic Pontine Glioma (clinicaltrials.gov)
    P1, N=53, Completed, Pediatric Brain Tumor Consortium | Active, not recruiting --> Completed
    Trial completion
    |
    Farydak (panobinostat)
    8ms
    Synergistic integration of histone deacetylase inhibitors apparently enhances the cytokine-induced killer cell efficiency in multiple myeloma via the NKG2D pathway. (PubMed, Clin Transl Immunology)
    We examined clinically relevant HDACis (panobinostat/LBH589 and romidepsin) alongside CIK cells derived from peripheral blood mononuclear cells across diverse MM cell lines (U266, RPMI8226, OPM-2 and NCI-H929). Our analyses provide sufficient evidence to consider this clinically forgotten instance (HDACis-CIK cell combination) as a therapeutic priority for MM treatment. Furthermore, we suggest that NKG2D/NKG2D-ligand interactions activating NK/NKT cells may contribute to enhanced myeloma cell lysis in response to HDACis treatment by CIK cells.
    Journal • IO biomarker • Epigenetic controller
    |
    IFNG (Interferon, gamma) • GZMB (Granzyme B) • MICA (MHC Class I Polypeptide-Related Sequence A) • MICB (MHC Class I Polypeptide-Related Sequence B) • NKG2D (killer cell lectin like receptor K1) • ULBP2 (UL16 Binding Protein 2)
    |
    Farydak (panobinostat) • Istodax (romidepsin)
    9ms
    Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) PRIME Trial (clinicaltrials.gov)
    P1, N=2, Terminated, OHSU Knight Cancer Institute | Active, not recruiting --> Terminated; Low accrual
    Trial termination
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • Avastin (bevacizumab) • Venclexta (venetoclax) • Lynparza (olaparib) • Mekinist (trametinib) • erlotinib • Gilotrif (afatinib) • Yervoy (ipilimumab) • Ibrance (palbociclib) • dasatinib • Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • carboplatin • Imfinzi (durvalumab) • sorafenib • Rozlytrek (entrectinib) • imatinib • sunitinib • everolimus • Nerlynx (neratinib) • Iclusig (ponatinib) • Kadcyla (ado-trastuzumab emtansine) • Cotellic (cobimetinib) • Lorbrena (lorlatinib) • Lenvima (lenvatinib) • bortezomib • doxorubicin hydrochloride • capecitabine • Verzenio (abemaciclib) • Xtandi (enzalutamide capsule) • Cabometyx (cabozantinib tablet) • albumin-bound paclitaxel • Stivarga (regorafenib) • abiraterone acetate • oxaliplatin • Aliqopa (copanlisib) • Vizimpro (dacomitinib) • Zydelig (idelalisib) • daunorubicin • Zolinza (vorinostat) • Idhifa (enasidenib) • Farydak (panobinostat) • Erivedge (vismodegib) • Nubeqa (darolutamide) • bicalutamide • leucovorin calcium • cabazitaxel • Vesanoid (tretinoin) • fluorouracil topical
    9ms
    ACTIVATE: Reducing the Residual Reservoir of HIV-1 Infected Cells in Patients Receiving Antiretroviral Therapy (clinicaltrials.gov)
    P1/2, N=17, Completed, Massachusetts General Hospital | Active, not recruiting --> Completed | N=34 --> 17
    Trial completion • Enrollment change
    |
    CD4 (CD4 Molecule)
    |
    Farydak (panobinostat) • Pegasys (pegylated interferon α -2a)
    9ms
    Discovery of novel anticancer flavonoids as potential HDAC2 inhibitors: virtual screening approach based on molecular docking, DFT and molecular dynamics simulations studies. (PubMed, 3 Biotech)
    Eleven out of 329 selected flavonoids were screened based on molecular docking studies, as they have higher binding affinities than the standard drugs vorinostat and panobinostat. Further experimental validation is needed to understand the selectivity of flavonoids as HDAC2 inhibitors. The online version contains supplementary material available at 10.1007/s13205-023-03912-5.
    Journal
    |
    HDAC2 (Histone deacetylase 2)
    |
    Zolinza (vorinostat) • Farydak (panobinostat)
    9ms
    Panobinostat sensitizes AraC-resistant AML cells to the combination of azacitidine and venetoclax. (PubMed, Biochem Pharmacol)
    The majority of acute myeloid leukemia (AML) patients respond to intensive induction therapy, consisting of cytarabine (AraC) and an anthracycline, though more than half experience relapse. In addition, panobinostat alone and in combination with VEN + AZA suppressed oxidative phosphorylation and/or glycolysis in AraC-resistant AML cells. These findings support further development of panobinostat in combination with VEN + AZA for the treatment of AraC-resistant AML.
    Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2L1 (BCL2-like 1)
    |
    MYC overexpression
    |
    Venclexta (venetoclax) • cytarabine • azacitidine • Farydak (panobinostat)
    9ms
    Phase I Study of Marizomib + Panobinostat for Children With DIPG (clinicaltrials.gov)
    P1, N=4, Terminated, Dana-Farber Cancer Institute | N=45 --> 4 | Trial completion date: Dec 2024 --> Feb 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jun 2024 --> Feb 2024; Withdrawal of support from BMS
    Enrollment change • Trial completion date • Trial termination • Trial primary completion date • Combination therapy
    |
    Farydak (panobinostat) • marizomib (NPI-0052)
    9ms
    EZH2 Inhibition Sensitizes IDH1R132H-Mutant Gliomas to Histone Deacetylase Inhibitor. (PubMed, Cells)
    We also found that, although the histone deacetylase inhibitor (HDACi) Panobinostat was less cytotoxic in IDH1R132H-mutated cells (either isolated from murine glioma or oligodendrocyte progenitor cells infected in vitro with a retrovirus expressing IDH1R132H) compared to IDH1-wild-type cells, combination treatment with Tazemetostat is synergistic in both mutant and wild-type models. These findings indicate a novel therapeutic strategy for IDH1-mutated gliomas that targets the specific epigenetic alteration in these tumors.
    Journal • Epigenetic controller
    |
    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
    |
    IDH1 mutation • IDH1 R132H • IDH wild-type • IDH1 R132
    |
    Tazverik (tazemetostat) • Farydak (panobinostat)
    9ms
    ORBIT: Optimizing Reversal of HIV Latency With Combination Therapy (clinicaltrials.gov)
    P1/2, N=49, Not yet recruiting, Erasmus Medical Center
    New P1/2 trial
    |
    lenalidomide • Farydak (panobinostat)
    10ms
    EphA2- and HDAC-Targeted Combination Therapy in Endometrial Cancer. (PubMed, Int J Mol Sci)
    To discover potential synergistic partners for EphA2-targeted drugs, we performed a high-throughput drug screen and identified panobinostat, a histone deacetylase inhibitor, as a candidate...The Axl-PI3K-Akt-mTOR pathway was also decreased by combination therapy. Together, our results highlight EphA2 and histone deacetylase as promising therapeutic targets for endometrial cancer.
    Journal • Combination therapy
    |
    AXL (AXL Receptor Tyrosine Kinase)
    |
    Farydak (panobinostat)
    10ms
    Phase I Study of Marizomib + Panobinostat for Children With DIPG (clinicaltrials.gov)
    P1, N=45, Active, not recruiting, Dana-Farber Cancer Institute | Trial primary completion date: Dec 2023 --> Jun 2024
    Trial primary completion date • Combination therapy
    |
    Farydak (panobinostat) • marizomib (NPI-0052)
    10ms
    A Novel Treatment Strategy Utilizing Panobinostat for High-Risk and Treatment-Refractory Hepatoblastoma. (PubMed, J Hepatol)
    Utilizing a preclinical HB pipeline, we demonstrate that panobinostat in combination with VI chemotherapy can induce an effective tumor response in models developed from high-risk, relapse, and treatment refractory HB patients.
    Journal
    |
    AFP (Alpha-fetoprotein)
    |
    irinotecan • vincristine • Farydak (panobinostat)
    10ms
    Novel combination of imipridones and histone deacetylase inhibitors demonstrate cytotoxic effect through integrated stress response in pediatric solid tumors. (PubMed, Am J Cancer Res)
    ONC201, ONC206, and ONC212 are imipridones showing pro-apoptotic anti-cancer response...Additionally, pediatric solid tumor cells were treated with single-agent therapy with histone deacetylase inhibitors (HDACi) vorinostat, entinostat, and panobinostat, showing cell killing with all 3 HDACi drugs, with panobinostat showing the greatest potency...Our results introduce a novel class of small molecules to treat pediatric solid tumors in a precision medicine framework. Use of impridones in pediatric oncology is novel and shows promising pre-clinical efficacy in pediatric solid tumors, including in combination with HDAC inhibitors.
    Journal • Epigenetic controller
    |
    ATF4 (Activating Transcription Factor 4)
    |
    Zolinza (vorinostat) • Farydak (panobinostat) • Jingzhuda (entinostat) • dordaviprone (ONC201) • ONC212 • ONC206
    11ms
    The methyltransferases METTL7A and METTL7B confer resistance to thiol-based histone deacetylase inhibitors. (PubMed, Mol Cancer Ther)
    To identify alternative mechanisms of resistance to romidepsin, we selected MCF-7 breast cancer cells with romidepsin in the presence of the P-gp inhibitor verapamil to reduce the likelihood of P-gp-mediated resistance. The resulting cell line, MCF-7 DpVp300, does not express P-gp and was found to be selectively resistant to romidepsin but not to other HDACis such as belinostat, panobinostat, or vorinostat. RNA sequencing analysis revealed upregulation of the mRNA coding for the putative methyltransferase, METTL7A, whose paralog, METTL7B, was previously shown to methylate thiol groups on hydrogen sulfide and captopril...We demonstrate that expression of METTL7A or METTL7B confers resistance to thiol-based HDACis and that both enzymes are capable of methylating thiol-containing HDACis. We thus propose that METTL7A and METTL7B confer resistance to thiol-based HDACis by methylating and inactivating the zinc-binding thiol.
    Journal • Epigenetic controller
    |
    ABCB1 (ATP Binding Cassette Subfamily B Member 1)
    |
    ABCB1 expression
    |
    Zolinza (vorinostat) • Farydak (panobinostat) • Istodax (romidepsin) • Beleodaq (belinostat) • captopril
    11ms
    Epigenetic-based combination therapy and liposomal codelivery overcomes osimertinib-resistant NSCLC via repolarizing tumor-associated macrophages. (PubMed, Acta Pharmacol Sin)
    Here, we developed a lactoferrin-modified liposomal codelivery system for the combination therapy of Osi and panobinostat (Pan), an epigenetic regulator of histone acetylation. We demonstrated that the codelivery liposomes could efficiently repolarize tumor-associated macrophages (TAM) from the M2 to M1 phenotype and reverse the epithelial-mesenchymal transition (EMT)-associated drug resistance in the tumor cells, as well as suppress glycolysis, lactic acid production, and angiogenesis. Our results suggested that the combination therapy of Osi and Pan mediated by liposomal codelivery is a promising strategy for overcoming Osi resistance in NSCLC.
    Journal • Combination therapy
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation
    |
    Tagrisso (osimertinib) • Farydak (panobinostat)
    11ms
    Safety and efficacy of a new high-dose regimen of panobinostat, gemcitabine, busulfan, and melphalan for 1st or 2nd salvage ASCT for refractory/relapsed or high-risk myeloma: Matched-pair comparisons with concurrent control cohorts. (PubMed, Am J Hematol)
    Trial patients had better PFS after either a 1st (p = .02) or a 2nd ASCT (p = .04) than matched-paired control patients. In conclusion, panobinostat/GemBuMel is effective for relapsed/refractory or high-risk myeloma patients, with better PFS than concurrent matched controls receiving melphalan or BuMel.
    Journal
    |
    SLC1A5 (Solute Carrier Family 1 Member 5)
    |
    gemcitabine • Farydak (panobinostat) • melphalan • busulfan
    11ms
    Androgen receptor blockade to activate NK cells and to upregulate the surface expression of HLA-E in prostate cancer cell lines. (ASCO-GU 2024)
    The pan HDAC inhibitors vorinostat (0.4 uM) and panobinostat (2.5 uM) were used to evaluate the regulation of HLA-E by epigenetics... The AR-responsive LNCaP cell line displayed an increase in surface expression of HLA-E upon treatment with enzalutamide (Enza) or darolutamide (Daro) ([C]: 12.1±1.3%, Enza: 22.3±3.3%, Daro: 19.1±1.1%, p=0.004)... Androgen inhibitors upregulate the expression of HLA-E in PCa cell lines by an AR-dependent mechanism regulated by epigenetics. ADT promotes peripheral blood patient-derived NK cell activation and upregulation of inhibitory NKG2A receptor. These findings support further investigative approaches targeting the HLA-E and NKG2A in mCRPC.
    Preclinical
    |
    AR (Androgen receptor) • CD8 (cluster of differentiation 8) • GZMB (Granzyme B) • HLA-E (Major Histocompatibility Complex, Class I, E) • KLRC1 (Killer Cell Lectin Like Receptor C1)
    |
    AR negative
    |
    Xtandi (enzalutamide capsule) • Zolinza (vorinostat) • Farydak (panobinostat) • Nubeqa (darolutamide)
    11ms
    Regulation of Hippo-YAP/CTGF signaling by combining an HDAC inhibitor and 5-fluorouracil in gastric cancer cells. (PubMed, Toxicol Appl Pharmacol)
    Histone deacetylase (HDAC) inhibitors diminish carcinogenesis, metastasis, and cancer cell proliferation by inducing death in cancer cells. Since combination treatment exhibits much higher anti-tumor potential than 5-FU alone, panobinostat effectively potentiates the anti-tumor efficacy of 5-FU. As a result, it is believed that panobinostat and 5-FU combination therapy will be useful as supplemental chemotherapy in the future.
    Journal
    |
    CDH1 (Cadherin 1) • VIM (Vimentin) • CASP9 (Caspase 9) • MMP9 (Matrix metallopeptidase 9) • CTGF (Connective tissue growth factor)
    |
    5-fluorouracil • Farydak (panobinostat)
    12ms
    Tumor Suppressive Mir-7 Targeting PSME3 Improves the Efficacy of Histone Deacetylases Inhibitors in Multiple Myeloma (ASH 2023)
    1S, KMS-11, RPMI-8226, H929, and U266) and patient samples to 10 nM panobinostat and 1 µM vorinostat for 48 h, we performed quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and observed significant downregulation in the expression of miR-7...1S and KMS-11 cells to the BRD4 inhibitor JQ1, which suppresses MYC, at concentrations of 50 and 100 nM for 48 h, qRT-PCR showed that the expression of miR-7 was significantly downregulated in these cell lines...The favorable combination effect of bortezomib with HDAC inhibitors could be due to the modulation of the miR-7- PSME3 axis... We revealed that miR-7 exerts anti-myeloma effects and that PSME3 is one of the targets of miR-7. miR-7 is an interesting microRNA because it is positively regulated by MYC, even though it is tumor-suppressive. Elucidating the role of miR-7 may lead to the re-discovery of HDAC inhibitors in MM therapeutic strategies.
    Clinical • Epigenetic controller
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BRD4 (Bromodomain Containing 4) • MIR7 (MicroRNA 7)
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    MYC expression • miR-7 expression
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    bortezomib • JQ-1 • Zolinza (vorinostat) • Farydak (panobinostat)