In conclusion, our work elucidates a coherent epigenetic pathway wherein entinostat activates AZGP1 to inhibit HCC metastasis. These findings nominate AZGP1 as both a critical mediator and a potential biomarker for entinostat-based therapy in advanced HCC.

P2, N=118, Recruiting, Zhejiang Cancer Hospital

Entinostat demonstrates strong anti-NSCLC activity by suppressing EGFR expression and downstream signaling, highlighting its potential as a therapeutic agent.

The short-term in vitro effects of 5d were modulated by a compensatory upregulation of autophagy. However, in long-term, this protective mechanism becomes insufficient to sustain tumor survival, resulting in strong antitumor efficacy in vivo in the CAM assay for both compounds even outperforming entinostat.

P1/2, N=49, Recruiting, National Cancer Institute (NCI) | N=30 --> 49

P1/2, N=55, Active, not recruiting, National Cancer Institute (NCI) | Trial primary completion date: Dec 2025 --> Nov 2026

Furthermore, high DHRS2 predicts better survival specifically in male patients, indicating sex-specific androgen involvement. Overall, these findings elucidate the epigenetic mechanism underlying the cisplatin-sensitizing effect of Entinostat, and identifies the DHRS2-AKR1C3-androgen axis as a potential target, particularly for male patients.

P1/2, N=29, Not yet recruiting, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Innovative treatments are being explored, including combination therapies such as metformin with 4SC-202, which show promise in reducing tumor cell migration and enhancing chemotherapy sensitivity. Additionally, nanoengineered formulations of cisplatin aim to improve drug delivery specificity and minimize systemic toxicity, offering a more patient-friendly approach...Addressing these areas is crucial for advancing prevention, enabling early diagnosis, and improving survival and quality of life for patients with OCSCC. This work supports ongoing progress in oral cancer research and clinical care.

We present a case of a man in his 70s with metastatic melanoma who experienced progression through sequential treatments including pembrolizumab in combination with the HDAC inhibitor entinostat, and ipilimumab. Transdifferentiation has been observed in a wide range of malignancies, but the molecular mechanisms of this phenomenon are poorly understood. This case provides the first molecularly validated example of melanoma to rhabdomyosarcoma transdifferentiation presenting as spatially segregated metastatic lesions with distinct, unmixed histologies and illustrates a mechanism of resistance to immunotherapy driven by phenotypic plasticity.

Among the compounds, domatinostat and entinostat exhibited the strongest affinities (ΔGbind ≈ -70 kcal/mol), in reasonable agreement with experimental data (r = 0.60). This supports an allosteric inhibition mechanism in which ligands lock HDAC3 into inactive conformations. Collectively, these findings offer mechanistic insights into HDAC3 regulation and highlight structural hot spots for the rational design of selective inhibitors with potential applications in targeted breast cancer therapy.

P2, N=50, Not yet recruiting, Sun Yat-sen University