P1, N=18, Not yet recruiting, First Affiliated Hospital of Zhejiang University

Moreover, Compound 14 demonstrated an impressive pharmacokinetic profile and exerted significant antitumor efficacy in the FLT3-ITD-positive AML xenograft mouse model (approximately 80% decrease in tumor mass). Also, biochemical blood analysis and histopathological studies revealed that Compound 14 demonstrated a good safety profile.

A co-delivery therapeutic strategy combining the pan-HDAC inhibitor belinostat (PXD101) with paclitaxel (PTX) was developed and evaluated in patient-derived cisplatin-resistant organoids and a platinum-refractory patient-derived xenograft (PDX) model. Modulation of p21 influenced cell-cycle re-entry, senescence burden, and responsiveness to PTX. These findings define an HDAC-p21-senescence axis that sustains chemoresistance in bladder cancer and provide preclinical evidence supporting combined epigenetic and antimitotic therapy as a strategy to overcome acquired drug tolerance.

P2, N=27, Recruiting, Tianjin Medical University Cancer Institute and Hospital | Not yet recruiting --> Recruiting

The ability of tumor cells to tolerate DNA damage limits the efficacy of many anticancer therapies. Our study reveals that pancreatic cancer cells enforce this resistance by sustaining expression of DNA damage response (DDR) genes through Class I histone deacetylases (HDACs). HDACs maintain genome-wide acetylation patterns required for efficient recruitment of the transcriptional machinery to DDR genes. Pharmacological HDAC inhibition disrupts this process and sensitizes pancreatic cancer cells to diverse DNA-damaging agents. To overcome systemic toxicity that limits translational potential, we further establish a bottlebrush prodrug nanoparticle platform that enables tumor-selective HDAC inhibition. Given the central role of the DDR in cancer, targeting HDAC-mediated DDR regulation through drug combinations and precision delivery may have broad therapeutic relevance across cancer types.

Furthermore, the blockade of pericyte differentiation by SAHA synergizes with propranolol, which inhibits endothelial differentiation of HemSCs, in a complementary manner. Additionally, SAHA promotes adipogenic differentiation of HemSCs and accelerates IH involution. Collectively, our work highlights the clinical significance of cell fate determination during IH progression, and establishes HDAC inhibition as a novel therapeutic option for IH through targeting pericyte differentiation of HemSCs, which provides a promising enhancement to current treatment strategies of refractory IH.

Exploratory in silico drug-response analyses identified differential predicted responses to entinostat, linsitinib, and VE-822 according to risk status and DUBR expression. This internally validated signature may support exploratory prognostic risk stratification of LSCC within the analyzed TCGA-derived cohort and may highlight DUBR as a candidate molecule for further biological investigation. Further validation in independent external cohorts and dedicated disulfidptosis functional assays is required before these findings can be considered generalizable.

P2, N=15, Not yet recruiting, Zhongshan Hospital (Xiamen), Fudan University

While Apicidin is more effective at maintaining the integrity of neurons and synapses, DMOG mainly stabilizes the vascular compartment. These results imply that better neuroprotection may be provided by combination therapy that targets both vascular and neuronal components.

Samples with low stemness and elevated pyroptosis showed enhanced inferred drug resistance, particularly to LBH589...CONCLUSION‌: This study highlights the molecular heterogeneity of gastric cancer, demonstrating how distinct cell death patterns and PTM features shape prognosis and drug sensitivity. The identified biomarkers and resistance profiles may provide valuable guidance for personalized therapeutic strategies.

P1, N=22, Completed, Beijing 302 Hospital | Trial completion date: Nov 2025 --> Mar 2026 | Trial primary completion date: Nov 2024 --> Dec 2025 | Not yet recruiting --> Completed

Representative compounds, including sulforaphane, erucin, puerarin, capsaicin, curcumin, trichostatin A, trichostatin C, and pinocembrin, highlight the potential of natural products to suppress tumor growth, promote apoptosis, impair migration, and enhance antitumor immunity through acetylation-related mechanisms...These findings support an evidence-oriented translational framework that prioritizes natural products according to mechanistic robustness, bladder cancer specificity, and combination potential. Overall, acetylation-targeting natural products represent a promising but still evolving therapeutic strategy for bladder cancer, warranting further subtype-specific, mechanistically rigorous, and translationally oriented investigation.