EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)

P2, N=900, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris

Combination of PRMT6 inhibitor EPZ020411, and EZH2 inhibitor GSK126 effectively suppresses breast tumour growth in the mouse xenografts...Consistently, PRMT6 mediated EZH2 R509 methylation is also confirmed in PRMT6-knockout mice. Our findings reveal that PRMT6 inhibitors might be promising combination therapy for EZH2-targeting cancer.

Structural analysis further identified deleterious nsSNPs affecting critical functional domains. CEP55, DLGAP5, and EZH2 are identified as RCD-associated biomarkers linked to immune suppression and immunotherapy resistance in HCC.

Emerging biomarkers, including CD74, and acquired resistance mechanisms after anti-C-C chemokine receptor 4 therapy further extend the translational relevance of recent pathologic findings. Overall, CTCL evolution appears to be a systemic process shaped by interactions between tumor-intrinsic genetic alterations and the skin microenvironment.

Furthermore, we found differential gene expression in different cells of the RB tissue. EZH2, UBLCP1, and HKDC1 overlapped with the identified instrumental variables (IVs) of immune cells to investigate potential molecular mechanisms by which immune cells participate in RB processes.

EZH2 is highly expressed in ATC, and its inhibitors EPZ6438 and GSK343 have anti-cancer potential. Two types of nanoparticles were successfully constructed with good sustained-release, targeting effects, and biosafety. They could improve the therapeutic efficacy and reduce toxic side effects, with GSK343-BSA@CS showing significant effects.

Nevertheless, the lncRNA-EZH2 axis presents a promising therapeutic avenue, with RNA-based strategies offering the potential to disrupt pathological lncRNA-EZH2 assemblies with greater precision than catalytic EZH2 inhibitors alone. This review synthesizes current mechanistic and functional insights into lncRNA-EZH2 regulation in GI cancers, organizing these interactions into key biological modules and highlighting emerging opportunities for diagnostic and therapeutic development.

In conclusion, in addition to supporting histology grading of EM, our findings highlight that EM-HG cases display more heterogeneous expression profiles than EM-LG with some features in between EM-LG and SM/BM. Further data is needed to explore the potential clinical utility EZH2 IHC in the clinical management of pleural mesothelioma.

This study aimed to investigate the combined use of ACD and TP (paclitaxel and cisplatin) against non-small cell lung cancer (NSCLC) in a orthotopic mouse model. In conclusion, the combination of ACD plus TP demonstrated potent anti-tumor and immunomodulation effects against NSCLC in association with reduced Treg activity and increased CD8+ T cell infiltration. Our study provides compelling preclinical evidence supporting ACD as an immunomodulatory adjunct to conventional NSCLC therapies.

Collectively, our findings identify PDRG1 as a clinically relevant oncogene in HCC and reveal an epigenetic mechanism by which PDRG1 cooperates with EZH2 to repress p21 and bypass senescence. The PDRG1-EZH2-p21 axis may represent a potential biomarker and therapeutic target for HCC.

Virtual screening and molecular dynamics simulations identified acetyldigitoxin (ADT) as a potent EZH2 inhibitor, demonstrating superior binding affinity (-10.90 kcal/mol) and complex stability compared to the known inhibitor GSK126...ADT induced G0/G1 cell cycle arrest and promoted apoptosis, accompanied by upregulation of pro-apoptotic genes (Bax, Caspase-3) and downregulation of anti-apoptotic (Bcl-2) and cell cycle (CyclinD1) genes. Our integrated findings position ADT as a repurposed drug candidate for targeting EZH2 in NSCLC, warranting further preclinical investigation including direct enzyme inhibition assays.