P2, N=63, Not yet recruiting, Peking University

P1, N=9, Terminated, Taipei Medical University Shuang Ho Hospital | Trial completion date: Dec 2024 --> Mar 2024 | Recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Mar 2024; The overall profile does not support development for metastatic colorectal cancer

The TRG-based risk model could predict HCC patient prognosis and closely linked to tumor immune environment, which could offer new possibilities for clinical treatment.

P2, N=32, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2025 --> Jun 2025 | Trial primary completion date: Jan 2025 --> Jun 2025

Representative drugs selected for further investigation included docetaxel, methotrexate, panobinostat, idarubicin, camptothecin, and pevonedistat. In conclusion, we identified several highly effective agents with potent anti-tumor activity in chondrosarcoma cells, independent of IDH mutation status. These agents represent promising candidates for chondrosarcoma therapy and warrant further preclinical investigation and potential inclusion in clinical trials.

We identified that histone deacetylases (HDACs) were prominent candidates, and subsequently identified that the HDAC inhibitors mocetinostat and pracinostat, as well as the combined HDAC-epidermal growth factor receptor inhibitor CUDC-101, were effective at radiosensitising cell models of HNSCC (FaDu, A253, UMSCC11b) through their impact on both spheroid growth and clonogenic survival assays. We also demonstrated that this combinatorial strategy leads to inhibition of the repair of DNA double-strand breaks through the neutral comet assay and γH2AX foci analysis using immunofluorescence microscopy, providing a mechanism of action through which HDAC inhibition functions in HNSCC radiosensitisation. We believe that this approach should be further investigated in preclinical models, in order to realise the full therapeutic potential of HDAC inhibition for the radiosensitisation of HNSCC, eventually leading to improved patient treatment efficacy and outcomes.

Our results demonstrate that OBP-801 promotes MHC class I presentation through LMP2 upregulation in tumor cells and thereby potentiates PD-1-targeting therapy. These data suggest that the combination of OBP-801 and anti-PD-1 treatment is a promising therapeutic strategy for ccRCC.

A253 cells were treated with human recombinant TNFα with or without HDAC inhibitor trichostatin A (TSA) and quisinostat (JNJ-26481585). The tricellular signaling pathway JNK inhibitor SP600125 and Hippo pathway MST1/2 inhibitor XMU-MP-1 prevented the apoptosis induced by treatment using TNFα or LSR-N-ab with HDAC inhibitors. Our findings indicated that treatment with TNFα or LSR-N-ab with HDAC inhibitors might be useful in the therapy for human SDC by enhancing apoptosis.

The combination of IDO1 and HDAC inhibitors represents a promising strategy for CRC treatment, and NP-I/P is a candidate for clinical trials.

P1/2, N=17, Active, not recruiting, Hackensack Meridian Health | Trial completion date: Nov 2024 --> Sep 2025 | Trial primary completion date: Nov 2024 --> Sep 2025

P1, N=24, Not yet recruiting, Italfarmaco

Patients with higher PPP1R14B expression responded more sensitively to drugs selumetinib and vorinostat, zebularine, azacitidine and VER155008. In summary, PPP1R14B was a potential diagnostic and prognostic biomarker of PCa and its high expression had closely association with tumor immune inhibition, proliferation and migration, providing a new target for drug therapy and immunotherapy in PCa.

Concomitantly, cells with high basal or treatment-induced HER2 expression showed most profound sensitivities towards HDACi. These findings may thus provide the basis for HDACi treatment as a therapeutic option (1) particularly valuable in HER2-amplified gastric cancer and (2) particularly useful in combination therapies with HER2 inhibitors.

Notably, genes commonly mutated in AITL, including RHOA, TET2, DNMT3A, and IDH2, were absent in this case. A review of the literature highlights the heterogeneous genomic landscape of AITL and the diversity of treatment options available, underscoring the importance of tailored approaches to overcome resistance and improve outcomes in this distinct lymphoma subtype.

P2, N=32, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Sep 2025

Dexamethasone (Dex) treatment resulted in a significant difference in cell migration rates in two CRC cell lines with disparate GR expression levels...Belinostat, the selected compound, was successfully validated for its potential to counteract the effects of GC-induced invasion in CRC cells in vitro...This study provides valuable insights into the molecular mechanisms underlying GC-induced metastasis, introducing newly repositioned compounds that could serve as potential adjuvant therapy to GC treatment. Furthermore, it opens avenues for exploring novel drug candidates for CRC treatment.

P1/2, N=89, Active, not recruiting, Fondazione Italiana Linfomi - ETS | Trial completion date: Oct 2026 --> Feb 2026

A high-throughput screening of 221 anti-cancer drugs identified five candidates-bortezomib, carfilzomib, doxorubicin, panobinostat, and romidepsin-that demonstrated low IC50 values, indicating potential efficacy in treating CS. These findings suggest that NCC-CS1-C1 is a valuable tool for both preclinical and basic research on high-grade conventional central CS.

P3, N=423, Active, not recruiting, Chipscreen Biosciences, Ltd. | Trial completion date: Mar 2025 --> Jun 2025

P2, N=45, Active, not recruiting, Sun Yat-sen University | Recruiting --> Active, not recruiting | Trial completion date: Sep 2023 --> Oct 2025 | Trial primary completion date: Sep 2022 --> Aug 2024

P1/2, N=89, Completed, Syndax Pharmaceuticals | Phase classification: P1b --> P1/2

P3, N=430, Recruiting, Chipscreen Biosciences, Ltd. | Not yet recruiting --> Recruiting

P2, N=22, Recruiting, National Institute of Neurological Disorders and Stroke (NINDS) | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

Such compounds hold the potential of improving the pharmacokinetic and pharmacodynamic profiles of HDAC inhibitors through the extension of the drug-target residence time. This perspective aims to capture this emerging paradigm and discuss its potential to improve the preclinical/clinical outlook of HDAC inhibitors in the coming years.

P2, N=100, Recruiting, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

In our study, the in vitro and in vivo experiments confirmed that chidamide and venetoclax synergistically inhibited the expression of MYCN and increased the expression of DKK3 by inhibiting the activity of HDAC and BCL2, inhibiting the Wnt/β-catenin signaling pathway and B-ALL cell proliferation. These findings indicate that the HDACi chidamide and the BCL2 inhibitor venetoclax can be used in combination to treat B-ALL, providing a new method and strategy for treating B-ALL.

CUDC-101 effectively enhances response to both proton and X-ray irradiation, in the triple-negative MDA-MB-231 cell line. This enhancement was most notable when CUDC-101 was combined with proton irradiation. This study highlights that CUDC-101 holds potential in the management of triple-negative breast cancer as monotherapy or in combination with protons or X-ray irradiation.

Additionally, panobinostat inhibited mitochondrial dysfunction and reduced oxidative stress in the spinal cords of EAE mice. In conclusion, our findings reveal that panobinostat significantly ameliorates experimental autoimmune encephalomyelitis in mice by inhibiting oxidative stress-linked neuroinflammation and mitochondrial dysfunction.

In vitro study showed that both the pan-HDAC inhibitor belinostat, class I and class IIa HDAC inhibitor valproic acid, and selective HDAC1 inhibitor parthenolide induce morphology alteration, proliferation inhibition, expression of neuronal markers including microtubule-associated protein 2, neuronal nuclei antigen, and synaptophysin in U87 cells. This study suggests that the HDAC inhibitors belinostat, valproic acid, and parthenolide can induce glioma cells to differentiate into neuron-like cells, with HDAC1/3/7 being the likely drug targets and HDAC1 potentially playing an important role in this.

In vivo experiments exhibited that AMH-4 was more effective than lartesertib and vorinostat in inhibiting the growth of NTERA-2 cL.D1 xenograft tumors with low toxicity. Overall, these results suggest that AMH-4 is an effective and low toxicity candidate for the treatment of testicular germ cell tumors.

Moreover, we observed a positive correlation between sample immune infiltration and sample resistance to elesclomol and panobinostat, whereas a negative correlation was found with venetoclax resistance. Our study enriches the current AML risk stratification and provides guidance for precision medicine in AML.

The relationship between DLBCL and glutathione-related genes was uncovered by our research, and six glutathione genes were linked to DLBCL. These genes might be used as diagnostic biomarkers or targets for treatment for DLBCL patients.

P2, N=49, Recruiting, Ruijin Hospital

P1/2, N=26, Active, not recruiting, Viracta Therapeutics, Inc. | N=130 --> 26

In vivo experiments also showed that PXD101 combined with radiotherapy could significantly inhibit the growth of GBM. This study provides experimental evidence for application of the novel HDACi PXD101 in the treatment of GBM, as well as new molecular markers and potential intervention targets that may be used in preventing GBM malignant progression and radioresistance.

Furthermore, the knockdown of IRF1 impaired the induction of PD-L1 expression in CCS cells. Therefore, the inhibition of HDAC1/3 has potential as a novel strategy to increase immunogenicity and as combination therapy with ICIs for CCS and melanoma.

P2, N=92, Recruiting, The First Affiliated Hospital of Soochow University | Trial primary completion date: Sep 2024 --> Sep 2025

Meanwhile, Entinostat treatment increased the serum level of the active form (intact) Fgf23 and reduced that of Pi and calcium (Ca) as well. This study raised a concern about the anabolic effects of Entinostat in bone, and demonstrated that Entinostat treatment causes hypophosphatemia and hypocalcemia by upregulating Fgf23 mRNA and increasing intact Fgf23 protein in serum.

Furthermore, these compounds caused hyperacetylation of histone H3 and α-tubulin, indicating robust cellular target engagement. Overall, in this work we have identified the HDAC inhibitor 18b with selective antiplasmodial and 9b, 9d, and 13f with selective anticancer activities, providing valuable hits for further drug development efforts aimed at creating derivatives with reduced cytotoxicity against non-cancer cells compared to quisinostat.

P1, N=45, Active, not recruiting, New Approaches to Neuroblastoma Therapy Consortium | Trial primary completion date: Jun 2023 --> Feb 2024

P2, N=44, Recruiting, Zhejiang Cancer Hospital | Not yet recruiting --> Recruiting

P1, N=8, Not yet recruiting, University of Minnesota