P2, N=51, Recruiting, Fudan University | Trial completion date: Sep 2025 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2026

P2, N=42, Recruiting, Fudan University Shanghai Cancer Center; Fudan University Shanghai Cancer Center

P2, N=57, Recruiting, Cancer Hospital Chinese Academy of Medical Sciences; Cancer Hospital Chinese Academy of Medical Sciences

P2, N=26, Not yet recruiting, ChongQing university cancer hospital; ChongQing university cancer hospital

P2, N=30, Not yet recruiting, The First Affiliated Hospital of Soochow University; The First Affiliated Hospital of Soochow University

P2, N=44, Not yet recruiting, Zhejiang Cancer Hospital

P1, N=26, Active, not recruiting, University of Michigan Rogel Cancer Center | Recruiting --> Active, not recruiting

Degradation of STAT3 by C210 enhanced the EBV-reactivating and anticancer capacity of suberoylanilide hydroxamic acid (SAHA). Depletion of XPB blocked SAHA-induced expression of late viral genes and production of infectious virions. These results elucidate a novel Hsp90 inhibitor targeting EBV lytic phase and extend the research on lytic induction strategy, which may offer reference value in the treatment of EBV-positive malignancies.

Additionally, NOP58 was linked to drug responses, including Methotrexate, Rapamycin, Sorafenib, and Vorinostat. Its expression level serves as a reliable prognostic biomarker and an actionable therapeutic target, advancing precision medicine for prostate cancer. Targeting NOP58 may enhance therapeutic efficacy and improve outcomes in oncology.

To evaluate the efficacy of a novel histone deacetylase inhibitor, chidamide, in combination with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (CR-CHOP) in the treatment of DEL. The most common grades 3-4 hematologic and nonhematologic toxicity were leukopenia (46.7%) and infection (21%), respectively. This long-term follow-up study indicates that CR-CHOP in untreated DLBCL with the DEL phenotype demonstrates high short-term efficacy and safety as well as promising survival outcomes.

P=N/A, N=25, Not yet recruiting, Peking University People's Hospital

In TRAIL-sensitive colon cancer cells (COLO205, HCT-116), P-cDR5 showed efficacy comparable to anti-DR5 mAb Drozitumab (DRO), but P-cDR5 outperformed DRO in TRAIL-resistant cells (HT-29), highlighting the importance of efficient receptor clustering...Combining P-cDR5 with valproic acid, a histone deacetylase inhibitor, resulted in further enhancement of apoptosis inducing efficacy, along with destabilizing mitochondrial membranes and increased sensitivity of TRAIL-resistant cells. These findings suggest that attaching multiple cDR5 peptides to a flexible water-soluble polymer carrier not only overcomes the limitations of previous designs but also offers a promising avenue for treating resistant cancers, pointing toward the need for further preclinical exploration and validation of this innovative strategy.

Additionally, the transcriptomes of these cells were reprogrammed to become highly responsive to chemotherapy (cisplatin), targeted therapy (trametinib), and epigenetic therapy (vorinostat). SCARA5 and AOX1 DNA promoters were hypermethylated in NSCLC, and SCARA5 methylation was identified as an epigenetic biomarker in tumors and liquid biopsies from NSCLC patients. Thus, we demonstrate that co-targeting G9a/DNMT1 is a promising strategy to enhance the efficacy of cancer drugs, and SCARA5 methylation could serve as a non-invasive biomarker to monitor tumor progression.

Our immunoepigenetic strategy harnesses IFNγ-mediated network to augment the cancer-immunity cycle, revealing a self-reinforcing STAT1-GSDME pyroptotic circuitry as the mechanistic basis for an ongoing phase-II trial to tackle ICB resistance (NCT05873244).

Chidamide combined with (+)-JQ-1 can inhibit the proliferation of MLL-r AML cells, inhibit the initiation of protective self-repair of these leukemia cells by inhibiting the DNA damage response pathway, and ultimately increase the apoptosis of these cells, but non- MLL-r AML cells have no similar results.

P1, N=93, Recruiting, Shanghai Junshi Bioscience Co., Ltd. | Not yet recruiting --> Recruiting

P1, N=34, Recruiting, University of Utah | Trial primary completion date: Aug 2024 --> Apr 2024

P1, N=23, Active, not recruiting, Ohio State University Comprehensive Cancer Center | Recruiting --> Active, not recruiting | N=10 --> 23 | Trial completion date: Dec 2022 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2024

Our study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.

P1, N=64, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

These findings demonstrate that ERAP1 inhibition combined with HDACi entinostat treatment and PD-1 blockade remodels the immune landscape of a non-immunogenic tumor such as NB, making it responsive to checkpoint immunotherapy.

P2, N=76, Recruiting, Ruijin Hospital | Trial primary completion date: Jun 2024 --> Jun 2025

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.

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.

P=N/A, N=400, Not yet recruiting, Ruijin Hospital

In this study, by conducting bioinformatics analyses as well as in vitro and in vivo experiments, we identified that NUSAP1 was significantly upregulated in LUAD, with a notable correlation with poorer overall survival, higher scores for immunogenicity and immune infiltration, as well as increased sensitivity to conventional chemotherapeutic drugs such as paclitaxel, docetaxel and vinorelbine in LUAD. Furthermore, we identified entinostat as a novel inhibitor of NUSAP1. Pharmacological targeting ERβ/NUSAP1 axis with fulvestrant (ERβ antagonist) or entinostat (novel NUSAP1 inhibitor) significantly reduced LUAD growth both in vitro and in vivo, which may represent effective alternative therapeutic strategies for patients with LUAD.

The results imply that MEF2C could be a valuable indicator for predicting outcomes and a possible target for immunotherapy for LUAD patients.

Mechanistically, our data point to NRP1 mediating this effect via the down regulation of migration machinery, namely SRC, FAK and ROCK1 expression/activity, that is in part, related to NRP1 interaction with integrin beta 1 (ITGB1). In summary, our data indicate that romidepsin down regulation of NRP1 significantly mitigates the ability of OS cells to seed the lung and establish metastases, and that targeting NRP1 or its effectors with selective inhibitors may be a viable means with which to prevent this deadly aspect of the disease.

When combined with the anti-HCC drug sorafenib, STR-V-53, showed greater in vivo efficacy...Transcriptomic analysis revealed that STR-V-53 primed HCC cells to immunotherapy through HDAC inhibition, impaired glucose-regulated transcription, impaired DNA synthesis, upregulated apoptosis, and stimulated the immune response pathway. Collectively, our data demonstrate that the novel HDACi STR-V-53 is an effective anti-HCC agent that can induce profound responses when combined with standard immunotherapy.

Our study demonstrated that Epi might be used as a HDAC1 inhibitor. Low-dose Epi could inhibit tumor progression by inducing cell ferroptosis in vitro and in vivo. Thus, Epi administration with lower concentration may be much more favorable and safer in the treatment with leukemia.

Acquired resistance to first-line chemotherapeutics was associated with autophagy mediated by BECN1 and regulated by TXNDC17, which can be reversed by SAHA.

The triple combination of entinostat, a BETi, and cisplatin is highly synergistic, reverses cisplatin resistance, and may thus serve as a novel therapeutic approach for bladder cancer.

Among them, compound 20 exhibited potential inhibitory activity on HDAC1, and demonstrated notable potency against RPMI-8226 cells with an IC50 value of 2.89 ± 0.43 μM, which was better than chidamide (IC50 = 10.23 ± 1.02 μM)...The ADME parameters calculation showed that 20 possesses remarkable theoretical drug-likeness properties. Taken together, these results suggested that 20 is worthy of further exploration as a potential HDAC-targeted anticancer drug candidate.

P2, N=30, Recruiting, Shanxi Province Cancer Hospital

Further, the cell death was more pronounced with SAHA treatment. Therefore, polydatin might be a better anticancer drug and can have a potential to replace SAHA in combinational therapeutic regimen.

Further molecular docking experiments illustrated the potential interactions between compound 11g and HDAC1. These findings suggested that the novel Tetrahydro-β-carboline-based HDACis could serve as a promising framework for further optimization as anticancer agents.

18A possessed similar HDAC inhibitory activity as MS-275 and potently suppressed CDC25 activity in vitro and the CDK1 dephosphorylation in cells. Additionally, 18A hindered the progression of S and G2/M phases, triggered DNA damage, and induced apoptosis. These findings underscore the potential of 18A as a targeted therapy for TNBC and warrants further preclinical development.

Furthermore, it was shown that DR4, DR5, and CHOP expressions were enhanced, and PI3K, Akt, ERK, STAT3, c-FLIPL, NF-κB, and BCR-ABL expressions were decreased by SAHA in K562 cells. Our study indicated that SAHA combined with TRAIL can increase the sensitivity of K562 leukemic cells to TRAIL by suppressing intracellular anti-apoptotic molecules and augmenting the expressions of DR4/DR5 and CHOP.

Finally, we showed that T cells contribute to in vivo tumor growth control in the presence of entinostat and trametinib combination treatment. Together, our findings reveal that HDAC3 is a druggable endogenous repressor of T cell recruitment into Kras mutant lung tumors.

Our results revealed a novel mechanism by which the HDACi SAHA potentiates CD8+T-cell-mediated antitumor activity through the HDAC1/JAK1/FGL1 axis, providing a rationale for the combined use of HDACis and immunotherapy.

ZDLT-1 as HDAC inhibitor could suppresses CRC cell growth in vivo and in vitro by triggering HIF-1α/Caspase-3/Caspase-9 pathway in promoting apoptosis, and triggering NF-κB/GSDMD/GSDME pathway in inhibiting tumor inflammation. Our results propose dehydroharmine derivative ZDLT-1 as a promising therapeutic small molecular agent for CRC.

Moreover, 19 exhibited better metabolic stability in vitro than SAHA. Our study demonstrated that compound 19 was a promising candidate for further preclinical studies.