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

Drug sensitivity analysis suggested therapeutic efficacy of Entinostat and 5-fluorouracil in this subgroup. Our study provides the first LLPS-associated prognostic framework for CRC, offering both a risk stratification tool and actionable therapeutic insights. The findings highlight LLPS as a critical molecular organizer in CRC pathogenesis and a potential target for precision oncology approaches.

P=N/A, N=52, Not yet recruiting, The First Affiliated Hospital of Chongqing Medical University; The First Affiliated Hospital of Chongqing Medical University

Simultaneous inhibition of the class I HDACs, HDAC1 and HDAC2, reduced FOXM1 expression and suppressed cell proliferation in high-grade meningiomas. Furthermore, the class I HDAC inhibitor domatinostat inhibited FOXM1 expression and cell proliferation in high-grade meningioma cells within a concentration range that was not toxic to normal cell lines. These results suggest the potential of domatinostat as a therapeutic option for the treatment of high-grade meningiomas, which are often difficult to manage clinically.

Molecular docking studies explored the interactions of these CRGs with entinostat. In conclusion, SEZ6, S100B, SPIB, and TFF1 were identified as significant prognostic genes in BRCA, providing insights into BRCA pathogenesis and potential personalized treatment strategies.

P1, N=57, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2025 --> Sep 2026

MS275 suppresses HCC cell proliferation and induces hepatocyte-like differentiation through PKM1-mediated metabolic reprogramming and ROS signaling. These findings support the potential of MS275 as a differentiation-based therapeutic strategy for HCC.

The expression of USP2 was positively correlated with sensitivity to small-molecule drugs, including entinostat, SB590885, and PF-562,271. USP2 acts as a negative regulator of gastric cancer progression. Consequently, USP2 has the potential to be utilized as a therapeutic target to improve the clinical prognosis and survival rates of patients.