P1, N=24, Recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Nov 2025 --> Mar 2026

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.

This uncovered consistent synergy between menin and lysine-specific demethylase 1 (LSD1) inhibition, including with the clinical agent iadademstat...In vivo, the combination produced potent antileukemic effects in both MOLM-13 and MLL-r patient-derived xenografts, markedly reducing leukemic burden and extending survival without overt toxicity. These findings identify LSD1 as a critical cofactor of the menin-MLL-LEDGF axis and establish concurrent menin and LSD1 inhibition as a mechanistically informed combinatorial therapeutic approach in MLL-r AML.

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.

The noncompetitive lysine-specific demethylase 1 (LSD1) inhibitors SP-2509 and SP-2577 are N'-(1-phenylethylidene)-benzohydrazides that display potent activity in Ewing sarcoma. This unique activity is instead associated with the N'-(2-hydroxybenzylidene)-benzohydrazide core and destabilization of Fe-S proteins. These findings reveal a novel mechanism of action for this class of compounds and raise additional questions regarding how EWSR1::FLI1 transcriptional regulation is linked to Fe-S biogenesis, the precise mechanisms of cell death, the biological features of susceptible cancer cells, and strategies for clinical translation.

P3, N=340, Recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Sep 2026 --> Jul 2027

KDM1A regulates CRC progression by modulating epithelial-mesenchymal transition (EMT), metabolism, and Wnt signaling. Targeting KDM1A with GSK2879552 represents a promising therapeutic strategy for CRC treatment.

P3, N=300, Recruiting, Merck Sharp & Dohme LLC | Trial completion date: Apr 2029 --> Mar 2028

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.

P1, N=25, Terminated, Incyte Corporation | Phase classification: P1b --> P1

P3, N=300, Recruiting, Merck Sharp & Dohme LLC | Trial primary completion date: Apr 2027 --> Sep 2027

Overall, LSD1 inhibition in tumor cells upregulates MHC-I expression and stimulates CXCL9 secretion by DCs to enhance antigen presentation and promote CD8+ T cell activation via the CXCL9-CXCR3 signaling axis, resulting in increased IFNγ production. This may have implications for treating poorly immunogenic and immunotherapy-resistant cancers.