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

Pharmacological inhibition of EZH2 using DS-3201 reproduced some of the molecular effects of viral infection, including increased mutp53 stability...Indeed, the inhibition of SIRT1 with EX-527 reversed mutp53 accumulation but restored c-Myc expression and increased extracellular IL-6 release...These results establish a mechanistic link between viral infection, epigenetic remodeling, and oncogenic dependency. They also suggest that targeting IL-6 signaling could represent a therapeutic vulnerability in HHV-6A-associated thyroid cancer, particularly in combination with SIRT1 inhibitors.

Our findings suggest that SOX-2 and EZH-2 may serve as biomarkers of aggressive behavior and a poor prognosis in primary epithelial MSGTs, providing potential opportunities for precision-targeted therapies.

Inhibiting Ca²⁺ signaling restored EZH2 function in CAR-T cells, significantly improving their antitumor activity. Our findings reveal the interdependent roles of EZH2 and Ca2+ signals in coordinating antigen-activated T-cell responses that mediate alloimmunity and tumor immunity.

P2, N=65, Recruiting, Evopoint Biosciences Inc.

Furthermore, combining GSK126 with everolimus, an mTOR inhibitor used clinically for pNENs, more effectively inhibited cell proliferation and tumor growth. In summary, Our findings reveal that the EZH2 inhibitor GSK126 induces ferroptosis by inhibiting the PI3K/AKT/mTOR pathway, suppressing pNENs progression, and HMGCS1 may mediate resistance to EZH2 inhibitors, offering new insights into pNENs treatment.

Fib-EXO increased the expression of vimentin, EZH2, DNMT1, TGF-β3, and c-MYC, and phosphorylated p65 protein, reduced COL1A1 and COL3A1 expression, and decreased miR-133a, miR-29, and miR-200c while increasing miR-21 in cultured MSMC, mirroring changes observed in fibroids. These findings indicate that Fib-EXO reprogram myometrial cells toward a fibroid-like phenotype characterized by increased proliferation, inflammation and fibrotic features thus contributing to fibroid propagation.

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.