Zolinza (vorinostat) / Merck (MSD) - LARVOL DELTA

Survival and response rates of histone deacetylase inhibitors in peripheral T-cell lymphoma: A comprehensive systematic review and meta-analysis of 67 studies. (ASH 2025) - "It has high relapses and unfavorable prognoses with first-line chemotherapy regimens (cyclophosphamide, doxorubicin, vincristine, and prednisone)...Currently, romidepsin, vorinostat, and belinostat have US FDA approval for the treatment of relapsed/refractory PTCL, while chidamide is approved in China but is not approved in the US...HDACi monotherapy in patients with R/R T cell lymphoma, demonstrated an ORR, with chidamide [42%; 95% CI: (0.148, 0.57), p-value = <0.00001, I2=85%] followed by romidepsin [30%; 95% CI: (0.25, 0.35), p-value = <0.00001, I2=35%], abexinostat [28%; 95% CI: (0.19, 0.37), p-value = <0.00001], belinostat [26%; 95% CI: (0.19, 0.33), p-value = <0.00001, I2=0%]... This meta-analysis demonstrates that HDACi has shown overall improved response rates and survival in PTCL patients. However, chidamide has higher response rates than romidepsin in previously treated (UT) patients. In R/R patients, complete remission is higher with romidepsin;..."

Epigenetic controller • Retrospective data • Review • Adult T-Cell Leukemia-Lymphoma • Extranodal Natural Killer/T-cell Lymphoma • Hematological Malignancies • Lymphoma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK

NF-κB is a potential therapeutic target for histone deacetylase inhibitor-resistant cutaneous T-cell lymphoma (ASH 2025) - "Histone deacetylase (HDAC) inhibitors, including vorinostat and romidepsin, are used clinically to restore the expression of tumor suppressor genes known to be epigenetically suppressed in CTCL...Finally, we confirmed that HDAC inhibitor-resistant cell lines displayed heightened sensitivity to inhibition of the NF-κB pathway by bortezomib, a proteasome inhibitor that prevents IκB degradation and thereby blocks NF-κB activation, and dimethyl fumarate, an immunomodulatory and anti-inflammatory drug that suppresses NF-κB signaling by reducing the nuclear translocation and phosphorylation of p65. Conclusion : These findings suggest that aberrant NF-κB activation is a central driver of HDAC inhibitor resistance in CTCL. Our results provide a strong rationale for exploring NF-κB inhibition as a therapeutic strategy to restore or enhance the efficacy of HDAC-inhibitor-based therapies, overcome HDAC inhibitor resistance, and improve the outcomes of patients with CTCL."

Epigenetic controller • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • T Cell Non-Hodgkin Lymphoma • Targeted Protein Degradation • BCL3 • EGR1 • EP300 • GATA3 • HDAC1 • HDAC2 • HDAC3 • HIC1 • RELA • SOX2 • STAT3

Developing epigenetic synergistic drug combinations with albendazole in paediatric acute myeloid leukaemia (ASH 2025) - "Similar anthelmintic agents, mebendazole (MBZ) and parbendazole (PBZ), have been reported to have effects on epigenetic regulators that alter C-MYB degradation (Walf-Vorderwülbecke et al...These epigenetic hits represent various target families such as HDAC inhibitors (vorinostat, panobinostat, and CUDC-101), BET inhibitors (OTX-015, PFI-1, and (-)-JQ), aurora kinase inhibitors (MK-8745 and JNJ-7706621), and DNA synthesis inhibitors (cytarabine)...HDAC inhibitors (vorinostat), BET inhibitors (OTX-015) and histone methyltransferase (MS023) were among the most represented epigenetic target families, indicating potential mechanism of action of the novel ABZ+epigenetic combination. The novel drug candidate ABZ was found to have remarkable anti-leukaemia efficacy in murine and human models of childhood AML in vitro and in vivo while having negligible effects in normal cells. Current work is focused on evaluating ABZ+epigenetic synergistic combinations that will be taken..."

Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Pediatrics • HOXA9 • IL1B • MEIS1

Trial in progress: A pilot study of venetoclax to AUGMENT epigenetic modification and chemotherapy in pediatric and young adult patients with relapsed and refractory Acute Myeloid Leukemia (ASH 2025) - P1 | "Epigenetic modification may mediate chemotherapy-resistantdisease through the silencing of tumor suppressor genes, and these alterations can be reversed withepigenetic-modifying agents, such as DNA methyltransferase inhibitors (azacitidine and decitabine) andhistone deacetylase inhibitors (vorinostat). Therefore, in T2016-003 (NCT02412475), we previouslycombined decitabine and vorinostat with fludarabine, cytarabine, and G-CSF (FLAG) for pediatric patientswith R/R AML...ClinicalTrials.gov Identifier: NCT05317403. This study may identify a novel strategy to decreasechemotherapy resistance and improve outcomes in R/R pediatric and young adult AML."

Clinical • IO biomarker • Acute Myelogenous Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Pediatrics • CEBPA • IDH1 • IDH2 • KMT2A • NUP98

Diagnostic and therapeutic patterns in cutaneous T-cell lymphomas (CTCL): Real-world data from the lymphoma epidemiology outcome-molecular epidemiology resource (LEO-MER) prospective cohort study. (ASH 2025) - P=N/A | "First-line (1L)systemic regimens were predominantly a) immunomodulatory agents (n=47, 29.3%); including oralretinoid (n=20), extracorporeal photopheresis (n=18), interferon (n=9) followed by b) chemotherapy(n=30, 18.7%) and c) targeted therapies (n=17, 10.6%) including Brentuximab Vedotin (n=6), Romidepsin(n=5), Mogamulizumab (n=3), Vorinostat (n=2) and Pralatrexate (n=1). We present initial data from our prospective LEO-MER cohort, a large US-based multicenter consortia.Our findings demonstrate variability in both diagnostic staging and treatment approaches for MF/SSpatients. The cohort demonstrated worse outcomes with high-risk disease and Black race/ethnicity.These findings warrant further study on the impact of underlying social determinant factors, given thevariability noted in this population."

Clinical • Real-world • Real-world evidence • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Mycosis Fungoides • Non-Hodgkin’s Lymphoma • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma • CD4

Neomorphic chromatin engagement and epigenetic reprogramming by the IKZF1 N159Y tandem duplication mutant in b-acute lymphoblastic leukemia (ASH 2025) - "Cytotoxicity assays were used to assess sensitivity to 3 epigenetic modulatorsincluding inhibitors of histone acetylation (A-485 and JQ1) or deacetylation (vorinostat). Cooperative binding with WT IKZF1 and binding at de novosites, not bound by WT, suggest partial dominant and neomorphic functions of the TD mutant. Ourfindings define a distinct chromatin regulatory program in IKZF1 N159Y leukemia and suggesttherapeutic vulnerability to epigenetic modulators targeting histone acetylation."

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • ABL1 • DUX4 • EP300 • IKZF1 • MCL1 • TGFB1

Vorinostat for GVHD prophylaxis in children, adolescents, and young adults (AYA) shows low incidence of acute GVHD and relapse with encouraging overall survival after allogeneic hematopoietic cell transplantation (HCT): A multisite, nonrandomized clinical trial (ASH 2025) - P1/2 | "Inhaploidentical-donor transplants, patients received post-transplant cyclophosphamide, mycophenolatemofetil, and tacrolimus, with vorinostat (60 mg/m2 twice daily) initiated on day +5 and continued throughday +30 post-HCT. Vorinostat for GVHD prophylaxis was well-tolerated with a low incidence of acute andchronic GVHD and encouraging 1-year OS in children and AYA patients. No dose-limiting toxicities orSAEs/AEs definitely attributable to vorinostat were observed. If validated in a larger cohort, vorinostatmay serve as a promising option for acute GVHD prevention in both HLA-matched and haploidenticaldonor transplants, without increasing relapse rates ."

Clinical • Acute Graft versus Host Disease • Acute Myelogenous Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Transplantation • HLA-B • HLA-C • HLA-DRB1

Functional Characterization of VS-186B, a Novel HDAC Inhibitor with Anticancer Activity. (PubMed, Int J Mol Sci) - "VS-186B was more cytotoxic than Curcumin and Vorinostat across most of the cell lines tested and was more specific to hematological cells...VS-186B exhibits promising anticancer potential as a selective HDAC inhibitor since it induces apoptosis in cancer cells without significant cytotoxicity to non-cancerous lines with a similar gene expression profile to known HDAC inhibitors. These findings support further development of VS-186B as an epigenetic treatment for leukemia/lymphoma."

Journal • Gene Therapies • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Oncology • ANXA5 • CASP3 • CASP7

Olaparib in Combination With Vorinostat in Patients With Relapsed/Refractory and/or Metastatic Breast Cancer (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: The Methodist Hospital Research Institute | Recruiting ➔ Active, not recruiting | Trial primary completion date: Sep 2025 ➔ Dec 2025

Enrollment closed • Trial primary completion date • Breast Cancer • Oncology • Solid Tumor • HER-2

Modeling and Translating Precision Therapies for NF1-Associated Tumors Across the Disease Spectrum (SNO 2025) - P1 | "Combining MEK and HDAC inhibitors (e.g., mirdametinib + vorinostat) led to durable tumor regression in vivo and supported our initiation of an early phase window of opportunity trial now open (NCT06693284). Two of our patient cases illustrate clinical potential: one with refractory, H3K27me3-negative MPNST had pain relief and reduced PET activity on selumetinib + vorinostat and remained alive more than two years after failure of all other therapies; another, an 11-year-old with NF1 and H3K27M-mutant spinal glioma, remained recurrence-free for over two years on the same combination. These integrated efforts advance several translational platforms to develop and implement targeted therapies across the NF1 tumor spectrum."

Brain Cancer • Genetic Disorders • Glioma • Neurofibromatosis • Neurofibrosarcoma • Oncology • Sarcoma • Solid Tumor • CDKN2A • CDKN2B • NF1 • SUZ12

Development and validation of a novel disulfidptosis-related gene signature for prediction of survival and immune microenvironment in osteosarcoma by WGCNA analysis. (PubMed, Discov Oncol) - "Besides, patients in the high-risk group exhibited lower IC50 values for vorinostat, elesclomol, OSI-906, pyrimethamine, thapsigargin, and doxorubicin, but a higher IC50 value for cisplatin, compared to those in the low-risk group, indicating differential drug sensitivities. In summary, we established a robust DRGs signature comprising BTN3A1, CEBPA, KCNAB2, TBX21, and MYC, which showed strong prognostic value and predictive potential for immune status and drug sensitivity in OS. Notably, functional experiments confirmed that BTN3A1 acted as a tumor suppressor in OS, highlighting it as a promising therapeutic target."

Gene Signature • IO biomarker • Journal • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • BTLA • BTN3A1 • CEBPA • LAG3 • PD-L1 • PD-L2 • TBX21

Histone Deacetylase Inhibition Enhances AQP3 Levels in Human Corneal Epithelial Cells and Corneal Wound Healing in Normoglycemic and Diabetic Male Mice. (PubMed, Cells) - "We hypothesized that the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) would improve corneal healing in diabetic mice...In vitro SAHA treatment of human corneal epithelial cells (HCECs) significantly increased protein expression of AQP3, important for corneal wound healing, but had no effect on ROS production. In conclusion, treatment with SAHA improved corneal wound healing, not only in male mice with diabetes and delayed wound healing but also in normoglycemic male mice; therefore, SAHA could potentially be repurposed as a topical treatment clinically to improve corneal wound healing."

Journal • Preclinical • Diabetes • Metabolic Disorders • Oncology • AQP3 • IL1B • TNFA

Identification and targeting oxidative phosphorylation/glycolysis to overcome anti-CSF-1R therapy resistance in glioblastoma. (PubMed, Cell Death Dis) - "To solve above problem, we have established a highly stable and refractory mouse G422TN-GBM model, in which temozolomide (TMZ) is the most effective monotherapy but can only slightly extend animal survival...TRAP-seq identified oxidative phosphorylation/glycolysis as anti-CSF1R therapy resistance mechanism, and it's combined with Cancer Therapeutics Response Portal (CTRP) identified piperlongumine (PL) or vorinostat (SAHA) as targeting drugs...In conclusion, targeting oxidative phosphorylation/glycolysis by PL or SAHA prominently improves therapeutic efficacy of PLX3397 + TMZ in GBM, which deserves priority for clinical trials. Our study also reveals that translatome profiling is efficient for uncovering drug-resistant targets."

Journal • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Antifibrotic Efficacy of Daclatasvir Against Pulmonary Fibrosis: Insights From Network Pharmacology, Molecular Docking, Dynamics, and Preclinical Evaluations. (PubMed, Chem Biodivers) - "The present study evaluated DAC in a bleomycin (BLM)-induced PF rat model, integrating network pharmacology, molecular docking, and molecular dynamics (MD) simulation to decipher its mechanisms...PCA analyses also confirmed complex stability, comparable to known inhibitors vorinostat and mocetinostat...Interestingly, a higher dose (12.4 mg/kg/day) showed reduced efficacy and increased lung index, indicating dose sensitivity. These findings suggest that DAC possesses dose-dependent antifibrotic activity in PF and warrants further exploration as a repurposable therapeutic candidate."

Journal • Preclinical • Fibrosis • Hepatitis C • Immunology • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • HDAC2 • HIF1A

The impact of histone deacetylase inhibition on neurobehavioural outcomes in preclinical models of traumatic and non-traumatic spinal cord injury: a systematic review. (PubMed, Front Immunol) - "Valproate was the most frequently studied HDAC inhibitor (n=20), followed by 4-phenylbutyrate (4-PBA; n=7) and RGFP966 (n=3). Trichostatin A, tubastatin A, entinostat, PCI-34051, scriptaid, CI-994, TMP269, vorinostat, 3-TYP, SW-100 and ACY1215 were each evaluated in a single study. Three studies used the sirtuin-1 (HDAC class III) inhibitor EX527 administered with an activator molecule: melatonin (n=1), MLN4924 (n=1) and oxymatrine (n=1)...These results support further investigation of HDAC inhibitors in preclinical studies before translation into clinical trials. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023477882."

Journal • Preclinical • Review • CNS Disorders • Orthopedics • Pain • Psychiatry • Reperfusion Injury • SIRT1

Anti-tumor effect of a histone deacetylase inhibitor on canine malignant melanoma. (PubMed, J Vet Med Sci) - "Vorinostat significantly suppressed cell proliferation through apoptosis and G0/G1 phase cell cycle arrest in vitro. These findings suggest that vorinostat might serve as a potential therapeutic agent for dogs with CMM, providing a basis for further in vivo studies."

Journal • Melanoma • Oncology • Solid Tumor

NANT 2021-02: Randomized MIBG With Vorinostat/Dinutuximab/Vorinostat + Dinutuximab (clinicaltrials.gov) - P2 | N=118 | Not yet recruiting | Sponsor: New Approaches to Neuroblastoma Therapy Consortium

New P2 trial • Neuroblastoma • Oncology • Solid Tumor

Selective HDAC4 inhibition by SP1-PTD promotes odontoblast differentiation. (PubMed, J Appl Oral Sci) - "SP1-PTD represents a first-in-class selective HDAC4 inhibitor that achieves robust pro-differentiation effects with an exceptional safety profile. By specifically targeting HDAC4-SMRT interactions, SP1-PTD overcomes limitations of conventional HDAC inhibitors and offers translational promise for dental regenerative medicine."

Journal • BGLAP • DSPP • HDAC4 • RUNX2

Modern Molecular Profiling Recontextualizes the RTOG-0539 Trial and Reveals Hidden High-Risk and Radiotherapy Resistant Meningiomas (SNO 2025) - "In addition, transcriptomic and epigenetic profiling revealed immune-related signatures in RT responders and upregulation of cell cycle–related pathways in RT non-responders, several of which overlapped with targets of vorinostat, a histone deacetylase inhibitor validated in aggressive meningioma models...However, molecular classification, particularly the Proliferative group, remains an independent and stronger predictor of RT response. These findings support integrating molecular biomarkers alongside modern grading frameworks to guide treatment and trial design in meningioma."

Brain Cancer • Meningioma • Solid Tumor • CDKN2A • CDKN2B • TERT

Mechanisms of emerging small molecule inhibitors for the treatment of newly diagnosed and recurrent glioblastoma (SNO 2025) - "Multikinase inhibitors such as Anlotinib performed the best in regards to prolonging survival (p < 0.01) and reduced toxicity (p < 0.05) in recurrent GBM patients. Newly diagnosed GBM patients experience greatest survival outcomes when treated with Valproic Acid (p < 0.01), although Vorinostat demonstrates the lowest rate of adverse events (p < 0.05)... Multikinase inhibitors carry great potential as additions to the existing GBM treatment regimen by providing synergistic tumor selectivity, limited adverse effects, greater treatment compliance, and improved prognosis. These findings highlight the need for continued preclinical and translational research to elucidate underlying mechanisms and support the design of biomarker-driven clinical trials evaluating SMI-based combination therapies in GBM."

Brain Cancer • Glioblastoma • Solid Tumor • PARP1

Novel small molecule inhibitor candidates for the treatment of newly diagnosed and recurrent glioblastoma (SNO 2025) - "For newly diagnosed GBM, the most frequently used SMI is DDRi Valproic Acid (VPA) which prolongs OS (p < 0.001) and PFS (p < 0.01), though DDRi Vorinostat demonstrates superior ORR (p < 0.01) and lower SAE (p < 0.05)...SMIs are commonly used in combination therapies, most often with another SMI or temozolomide (TMZ), with DDRis performing best while in combination with TMZ (p < 0.01). SMIs such as Anlotinib and VPA carry great potential as additions to the existing GBM treatment regimen by providing synergistic tumor selectivity, limited adverse effects, greater treatment compliance, and improved prognosis. These findings highlight the need for continued preclinical and translational research to elucidate underlying mechanisms and support the design of biomarker-driven clinical trials evaluating SMI-based combination therapies in GBM."

Brain Cancer • CNS Tumor • Glioblastoma • Solid Tumor • FGFR

Targeting H3K27M protein with inhibitors of histone deacetylases in H3K27-altered diffuse midline gliomas (SNO 2025) - "Importantly, we have recently shown that some HDACi (including panobinostat, pracinostat/SB939, vorinostat and entinostat) lead to the reduction in the H3K27M protein levels. We are hoping that our studies may pave the way for new therapeutic strategies for patients with DMGs, aiming at eradication of detrimental H3K27M oncohistone protein. The study is supported by the Sonata Bis-14 grant (2024/54/E/NZ3/00480) awarded by the National Science Centre, Poland."

Epigenetic controller • Brain Cancer • Diffuse Midline Glioma • Glioma • High Grade Glioma • Solid Tumor

Synergistic Effects of HDAC Inhibition and Hippo Signaling Pathway Regulation in Glioblastoma (SNO 2025) - "In this study, we evaluated the therapeutic impact of combining the HDAC inhibitor SAHA (suberoylanilide hydroxamic acid) with Verteporfin, a Hippo signaling pathway regulator, in patient-derived GBM tumor spheres (TS13-64 and TS15-88). Our findings suggest that combined modulation of HDAC activity and Hippo pathway signaling represents a promising therapeutic strategy for GBM. This dual-targeted approach may overcome current treatment resistance and improve clinical outcomes in GBM patients."

Brain Cancer • Glioblastoma • Solid Tumor

EXAMINING THE THERAPEUTIC EFFECT OF TBL1/ β-CATENIN TARGETED COMBINATION THERAPIES ON METASTATIC OSTEOSARCOMA (CTOS 2025) - "Targeting the TBL1/β-catenin axis with Tegavivint in combination with Ponatinib or Vorinostat may offer a more effective treatment strategy for high-risk OS. These combinations show promise in overcoming drug resistance and improving outcomes for patients with limited options."

Combination therapy • Metastases • Oncology • Osteosarcoma • Sarcoma • Solid Tumor • CTNNB1 • MYC • TBL1XR1

Comparative Study of Histone Deacetylase Inhibitors for Radiation Protection Using Survival Outcomes in a Mouse Model. (PubMed, Biol Pharm Bull) - "Male ICR mice received 7.5 Gy TBI followed by a single administration of valproic acid (VPA; 300 or 600 mg/kg), sodium butyrate (NaB; 500 or 1000 mg/kg), trichostatin A (TSA; 0.5 or 1.0 mg/kg), vorinostat (10 or 50 mg/kg), panobinostat (25 or 50 mg/kg), givinostat (5 or 10 mg/kg), or entinostat (25 or 50 mg/kg). VPA's efficacy may reflect a combination of effects on DNA repair, inflammation, and redox regulation rather than HDAC inhibition alone. These findings suggest VPA to be a promising candidate for radioprotection and emphasize the need for further studies to optimize dosing and explore underlying mechanisms."

Clinical • Journal • Preclinical • Inflammation