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

First in class Anti-CLEC-1A myeloid checkpoint antibodies for the treatment of solid tumors with monotherapy and combination therapy efficacies (AACR 2025) - "Although their biological activities following interaction with CLEC-1 remain to be fully investigated, we observed that a cell stress induced by radiation or by different chemotherapeutic class agents such as cyclophosphamide (CPA), oxaliplatin, vorinostat and others, increase the expression of CLEC-1 ligand(s) on necrotic and live cells. Moreover, we confirmed also the therapeutic effect of these anti-CLEC-1 antibodies in combination with CPA in the ectopic MC38 model (n=18, 2 independent experiments). Altogether, our results further dissect the mechanism of action of the myeloid checkpoint CLEC-1 in its ability to impair anti-tumor immunity and support its target with antagonist antibody for cancer immunotherapy."

Combination therapy • IO biomarker • Monotherapy • Fibrosarcoma • Liver Cancer • Oncology • Sarcoma • Solid Tumor • TRIM21

Development of MYCN/MYC inhibitors (AACR 2025) - "MYCN amplification and overexpression generate driver signals in the childhood cancers, neuroblastoma (NB), medulloblastoma (MB) and diffuse intrinsic pontine glioma (DIPG).Methods and We previously reported a small molecule compound, SE486-11, which reduced MYCN protein levels in combination with suberoylanilide hydroxamic acid... Collectively, our data suggest that MYCN and c-MYC are the direct molecular targets of UNSW-SC compounds. These compounds have strong potential to serve as specific targeted therapy to treat MYCN/c-MYC driven paediatric and adult cancers."

Brain Cancer • CNS Tumor • Diffuse Intrinsic Pontine Glioma • Glioma • Medulloblastoma • Neuroblastoma • Oncology • Solid Tumor • MYC • MYCN

HMGA1 Epigenetic Regulators Drive Relapse in Pediatric B-Cell Leukemia By Amplifying ETV5 and Stemness Networks (AACR 2025) - "In PDX models with pB-ALL blasts from relapse, we found that vorinostat enhances responses to standard B-ALL therapy (dexamethasone, vincristine), depleting circulating blasts and disrupting leukemic engraftment. Our findings reveal HMGA1 as an epigenetic switch that activates ETV5 and HSC gene networks in relapsed pB-ALL and rational therapeutic target to treat or prevent relapse."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ETV5 • HMGA1

Establishing patient-derived xenograft organoids (PDXOs) from renal cell carcinoma for drug screening and identification of treatment-induced vulnerabilities (AACR 2025) - "Cell viability assays evaluated six PDXOs' responses to Sunitinib (one of the stand-of-care drugs in RCC). Results were correlated with patients' clinical outcomes for three cases of PDXOs with BAP1 mutations (BAP1MUT) and wild-type BAP1 (BAP1WT ) were treated with Olaparib (Poly(ADP-ribose) polymerase (PARP) inhibitor) and Vorinostat (Histone deacetylase (HDAC) inhibitor)...BAP1 mutations in PDXOs also revealed drug vulnerabilities, highlighting increased sensitivity to Olarapib and Vorinostat. These findings underscore the value of PDXOs as robust tools for predicting patient responses to therapy and exploring target treatments for ccRCC."

Clinical • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • BAP1

Development of Pt-HDACi complexes to enhance potency and selectivity for advanced cancer therapy (AACR 2025) - "Particularly, L19 and L21 with a heterocyclic ring in the linker showed the highest potency, with IC50 values significantly lower than the FDA-approved Vorinostat and Panobinostat. Molecular docking studies further supported these findings by revealing stronger binding affinity towards the HDAC enzymes, demonstrating similar trend in inhibition and potency toward cancer treatment."

Metastases • Oncology • NCOA4

Gene expression and bioinformatics profiles of four different cancer cells following treatment with HDAC inhibitor SAHA (AACR 2025) - "Our study demonstrates some commonality in the DEGs and the impact of HDAC inhibition with SAHA in four different human cancer cells compared with normal cells. Our findings provide new insights into the network and the interactions of significantly altered gene expressions that may eventually impact the growth abilities of cancer cells. Our findings also highlight some of the potential molecular targets and related signaling pathways."

Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • DNMT3A • HDAC3 • NSD1

PCNA and histone deacetylase targeted inhibitors in cutaneous T-cell lymphoma (AACR 2025) - "Inspired by phosphoproteomic analyses of AOH1996-treated cells, we investigated its potential in combination therapy with the histone deacetylase inhibitors (HDACi) vorinostat and belinostat. Enhanced growth inhibition was also observed when AOH1996 was combined with other HDACi, such as domatinostat and panobinostat. These findings highlight the therapeutic potential of AOH1996 in combination with HDACi, particularly for CTCL, and pave the way for further exploration of this approach in cancer treatment."

Epigenetic controller • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • PCNA

N-acetyl-L-cysteine (NAC) sensitizes psammaplin A induced DNA damage in malignant hematologic cells by enhancing HDAC inhibition (AACR 2025) - "PsA is enhanced by NAC to inhibit tumor growth in MOML13 xenograft models without causing toxicity. These data support that NAC enhances PsA effect by increasing intracellular GSH which reduces PsA into a HDAC inhibiting monomer with increased cancer cell growth inhibition."

Hematological Malignancies • Oncology

Discovery and in vitro characterization of FGFR/HDAC dual inhibitors for FGFR-driven cancer (AACR 2025) - "In this model, the inhibitory efficacy of pemigatinib (an FDA approved FGFR 1-3 inhibitor) was significantly attenuated, whereas vorinostat (an FDA approved pan-HDAC inhibitor) maintained its efficacy. In summary, these in vitro studies have resulted in several compounds that warrant further development for lead optimization. They also suggest that FGFR/HDAC dual inhibitors may be an option for overcoming bypass resistance in FGFR-driven tumors."

Preclinical • Biliary Cancer • Bladder Cancer • Cholangiocarcinoma • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • EGFR • ERBB3 • FGFR2 • FGFR3 • FGFR4 • HER-2 • MET • NRG1

Targeting TNBC with a novel vorinostat conjugate that selectively inhibits and degrades HDAC3 and HDAC6 (AACR 2025) - "AH3 has better tumor growth inhibition ability than verinostat in MDA-MB-231 xenograft model. AH3 is novel since both degrades and acts as an HDAC3/HDAC6 selective inhibitor with enhanced selectivity and antitumor ability against TNBC."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CFLAR • HDAC3

Epigenetic approaches to deliver a targeted radiotherapy for triple negative breast cancer (AACR 2025) - "Remarkably, in MDA-MB-231 cells, Cu(DDC)2 combined with the VCP inhibitor CB5339, significantly increased NIS expression and radioiodide uptake leading to a prominent decrease in cell proliferation and survival. These studies, along with ongoing drug strategies in TNBC xenograft and PDX tumors, combine to support the concept that SLC5A5/NIS expression can be restored and offer the possibility of promoting radioiodide as a novel BrCa radiotherapy."

Breast Cancer • Endocrine Cancer • Oncology • Solid Tumor • Thyroid Gland Carcinoma • Triple Negative Breast Cancer • PRAME • RARA • TNFA

Transcriptomics of proviral latency reversal in reservoirs of youth with perinatal HIV-1 (IMMUNOLOGY 2025) - "Combined GS-9620+SAHA treatment uniquely activated TNFα, interferon, and estrogen pathways. These findings reveal that HIV-1 reservoirs in perinatal infections are susceptible to reactivation through LRAs, mediated by IFNs, TGF-β, TNFα, and IL-2, providing insights into latency reversal mechanisms in AdWPH."

Human Immunodeficiency Virus • Infectious Disease • CD4 • CD69 • IFNA1 • IFNG • IL2 • IL2RA • IL6 • TGFB1 • TNFA

The role of Vpr in a primary CD4+ T-cell model of HIV-1 latency (IMMUNOLOGY 2025) - "We sought to determine how the cytotoxic HIV-1 protein Vpr, both alone and in combination with the HDAC inhibitor vorinostat (VOR), regulates HIV-1 latency establishment...Vpr may therefore play an important role in shaping the latent reservoir. An improved understanding of how both viral and host factors affect latent reservoir formation will aid in the development of new latent HIV-1 reservoir-targeting therapies."

Human Immunodeficiency Virus • Infectious Disease • CD4

Immune competent 3D pancreatic adenocarcinoma (PDAC)-on-chip model for preclinical drug discovery (AACR 2025) - "To date, targeted treatment regiments are not available, leaving only cytotoxic chemotherapy with gemcitabine or FOLFIRINOX as the first-line-treatment for patients who are ineligible for surgical resection...As one example, we identified vorinostat, a histone deacetylase inhibitor already approved for cutaneous T cell lymphoma, significantly reducing PDAC spheroid viability in a dose dependent manner without impacting the vascular integrity...We show that monocytes applied through the vasculature invade through the endothelial barrier and migrate into CAF rich areas, where they differentiate to M2-like macrophages upregulating CD163 and loosing CD86 and HLA-DR expression. We now use this system to study T cell invasion, as well as direct vascularization of PDAC tumors."

Preclinical • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • T Cell Non-Hodgkin Lymphoma • CD163 • CD86

Evaluation of the effects of MDM2 inhibitor and epigenetic modifiers in combination with AURKB inhibitors for treating lung cancer (AACR 2025) - "We also examined the anti-cancer effects of RG-7388, SAHA, CM-272, and Barasertib (an AURKB inhibitor), in modulating cell cycle regulation...Our findings confirm that AURKB levels can be down-regulated by using the combination of MDM2 inhibitors and epigenetic regulators such as SAHA and CM-272. However, the therapeutic efficiency of these combinations needs to be verified using in vivo experimental models."

Combination therapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • ALDH1A1 • AURKB • BCL2L1 • CASP7 • CCNA2 • CDC25C • CDK4 • CDK6 • CDKN1A • GNRP • PARP1 • XIAP

Histone deacetylase inhibitor, Vorinostat, reverses EGFR-TKI resistance in lung adenocarcinoma via degradation of MET (AACR 2025) - "Next, to explore the mechanism(s) through which VS enhances MET-dependent cell death, we performed several experiments including 1) real-time RT-PCRs and western blots to discern if VS regulates the expression of MET at transcriptional or translational level; 2) cycloheximide chase assays to examine the impact of VS on MET protein stability; 3) treatment with RGFP109, a HDAC1/HDAC3 selective inhibitor, to specify which HDAC(s) may be involved in this process. Our study suggests that VS promotes cell death of LUAD cells with amplification of MET via inducing HDAC1/3-mediated MET protein degradation. In combination with Osimertinib, VS reverses the amplification of MET-induced TKI resistance in LUAD cells. This combination might be therapeutically exploitable to overcome acquired TKI resistance caused by MET amplification in NSCLC patients."

Epigenetic controller • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • HDAC3 • MET

Combination therapy of HDAC inhibitors with HSP90 and TRAP1 targeting the hypoxia pathway in triple-negative breast cancer (AACR 2025) - "In this study, we evaluated the efficacy of novel drug combinations involving Heat Shock Protein 90 inhibitor (HSP90i) NDNB-25, Tumor Necrosis Factor Receptor-Associated Protein 1 inhibitor (TRAP1i) NDNT-34, and histone deacetylase inhibitors (HDACis) such as CAY10603, suberoylanilide hydroxamic acid (SAHA), and Valproic acid (VPA)...Fluorescent imaging revealed more distribution of hypoxia signals using a labeled hypoxia probe and the localization of TRAP1i, tagged with rhodamine B, in TNBC-derived mammospheres compared with luminal subtype. These findings suggest that combining epi-drugs and targeted therapies to modulate the hypoxia pathway could inform the development of innovative clinical strategies against TNBC."

Combination therapy • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CDC37 • EPAS1 • HIF1A • HSP90AA1 • TNFA

Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma (clinicaltrials.gov) - P2/3 | N=790 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Trial completion date: Mar 2028 ➔ Sep 2028

Trial completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • BCL2

Reduced EZH1/2 expression in imipridone-treated cells correlates with synergy following combinations with EZH1/2 or HDAC inhibitors in diffuse glioma and other tumors. (PubMed, Am J Cancer Res) - "Small molecule imipridones including ONC201, ONC206 and ONC212 have anti-cancer activity mediated in part through the integrated stress response, induction of TRAIL and its receptor DR5, and activation of mitochondrial caseinolytic protease ClpP with impaired oxidative phosphorylation...RNA-seq showed ONC201 and EHZ2i tazemetostat-treated cells have similar transcriptional profiles and share overlap of top regulated genes...ONC201 and EZH2i share similar targets and actions on tumors. Synergistic combinations of imipridones plus EZH1/2i or imipridones, EZH2i and HDACi merit further investigation."

Journal • Brain Cancer • Breast Cancer • CNS Tumor • Gastric Cancer • Gene Therapies • Genito-urinary Cancer • Glioma • Lung Cancer • Oncology • Prostate Cancer • Small Cell Lung Cancer • Solid Tumor • EZH2

VALOR study: A phase II trial of vorinostat to augment response to 177Lutetium-PSMA-617 in the treatment of patients with PSMA-low metastatic castration resistant prostate cancer. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT06145633 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Metastases • P2 data • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor

High-Dose or Low-Dose Vorinostat in Combination With Carboplatin or Paclitaxel in Treating Patients With Advanced Solid Tumors (clinicaltrials.gov) - P1 | N=20 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Apr 2025 ➔ Apr 2026

Trial completion date • Oncology • Solid Tumor

Targeting Latent HIV Reservoirs: Effectiveness of Combination Therapy with HDAC and PARP Inhibitors. (PubMed, Viruses) - "Latently infected J-Lat cells and dual-fluorescent HIV-infected primary CD4 T cells were treated with the HDAC inhibitor (vorinostat) and one of four PARP inhibitors (olaparib, rucaparib, niraparib, or talazoparib). These findings demonstrate that combining HDAC and PARP inhibitors augments latency reversal and reservoir reduction. With both the HDAC inhibitors and PARP inhibitors used in this study approved by the FDA for cancer treatment, this combination therapy holds strong potential for rapid clinical integration, contingent upon the confirmation of efficacy and safety in ongoing in vivo studies."

Journal • Human Immunodeficiency Virus • Infectious Disease • Oncology • CD4

MIBG With Dinutuximab +/- Vorinostat (clinicaltrials.gov) - P1 | N=45 | Completed | Sponsor: New Approaches to Neuroblastoma Therapy Consortium | Active, not recruiting ➔ Completed

Trial completion • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • CD34

Effect of Vorinostat on ACTH Producing Pituitary Adenomas in Cushing s Disease (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: National Institute of Neurological Disorders and Stroke (NINDS) | N=22 ➔ 0 | Trial completion date: Dec 2025 ➔ Apr 2025 | Recruiting ➔ Withdrawn | Trial primary completion date: Dec 2025 ➔ Apr 2025

Enrollment change • Trial completion date • Trial primary completion date • Trial withdrawal • Cushing’s Disease • Endocrine Disorders • Pituitary Gland Carcinoma

Exome-wide association study reveals 7 functional variants associated with ex-vivo drug response in acute myeloid leukemia patients. (PubMed, BMC Med Genomics) - "We identified exome-wide significant (p < 9.02 × 10- 7) associations for rs113985677 in CCIN with tamoxifen response, rs115400838 in TRMT5 with idelalisib response, rs11878277 in HDGFL2 with entinostat, and rs2229092 in LTA associated with vorinostat response. Additionally, a significant association of rs35704242 in NIBAN1 was associated with the combined response for nonchemotherapy medicines (p = 2.51 × 10- 8), and BI.2536, gefitinib, and belinostat were identified as the central traits. Our study represents the first EWAS to date on ex-vivo drug response in AML and reports 7 new associated loci that help to understand the anticancer drug response in AML patients."

Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology