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

Our analyses reveal that Tan IIA regulates 13 core targets of Dox cardiotoxicity-with enrichment in pathways including canonical cancer and small cell lung cancer pathways-and that six of these targets exhibit high binding affinity for Tan IIA or Dox; notably, machine learning prioritized the histone methyltransferase EZH2 as the central target for Tan IIA's anti-TNBC activity, and we further show EZH2 is highly expressed in breast invasive carcinoma (BRCA) tissues and correlates positively with infiltration of immune cells (e.g., B cells, CD4⁺ T cells) and expression of immune-related molecules (including immunosuppressors and MHC-associated antigen-presenting molecules). Collectively, these findings demonstrate that Tan IIA may mitigate Dox cardiotoxicity via modulation of targets such as APAF1, AR, and TERT (and their associated signaling cascades) while targeting EZH2 to exert anti-TNBC effects, providing a mechanistic framework for repurposing Tan IIA to improve the safety and efficacy of Dox-based BC therapy.

P2, N=0, Withdrawn, Epizyme, Inc. | N=55 --> 0 | Not yet recruiting --> Withdrawn

In summary, both EZH2 inhibitors showed therapeutic potential in comparison to cisplatin based on cellular and molecular readouts. Additionally, EPZ6438 showed a greater efficacy and higher sensitivity towards HPV+ cells, which was further supported by preliminary in vivo results from the chorioallantoic membrane assay.

Rescue experiments using the EZH2 inhibitor GSK126 assessed the functional output of the OLFML2A-EZH2 axis via CCK-8, EdU assays...Comprehensive proteomic and molecular biology analyses further indicated that OLFML2A may play a role in cell cycle regulation through the modulation of EZH2. Our findings suggest that OLFML2A may facilitate cell cycle progression by regulating EZH2, implicating it as a potential therapeutic target for triple-negative breast cancer.

This study aimed to investigate the effectiveness of sodium dichloroacetate (NaDCA) and a sodium valproate NaDCA combination (NaVPA-NaDCA) on formed patients' primary cell tumors on the chick embryo chorioallantoic membrane (CAM). The treatment with NaVPA-NaDCA significantly reduced the expression of PCNA, p53, EZH2 and vimentin in the tested tumors. Data demonstrated an antitumor effect of NaVPA-NaDCA in an in vivo model of a patient's primary glioblastoma cells.

CHOP or CHOP-like regimens have long been the standard frontline therapy; however, the addition of brentuximab vedotin has improved overall survival and established a new standard of care for CD30-positive PTCL...Epigenetic modulators, including histone deacetylase inhibitors and an EZH1/2 inhibitor, have demonstrated particularly high activity in TFH-derived subtypes, supporting the integration of biomarker-driven patient selection as a path toward precision medicine in PTCL. This review summarizes current insights into the genetic landscape, recent clinical advances in novel agents, and future perspectives on therapeutic stratification, highlighting the need to translate molecular insights into durable clinical benefits for patients with PTCL.

Similar to EZH2, NF90 promotes cell-cycle gene expression, is upregulated in advanced PCa, and is associated with poor clinical outcomes. Collectively, our findings uncover RNA-mediated protein interactions as a central mechanism underlying PRC2-independent transcriptional activation by EZH2 and establish NF90 as a major EZH2 coactivator, a master regulator of the cell cycle, and a promising therapeutic target in advanced PCa.

While H3K27M mutations are hallmark features of diffuse midline gliomas, rare cases of posterior fossa ependymomas harboring these mutations have been reported. Recent studies suggest molecular similarities between diffuse midline gliomas and posterior fossa ependymomas expressing H3K27M and EZHIP, potentially reflecting shared hindbrain developmental programs in their biological origins.

Our lead ASO successfully corrects aberrant splicing and NMD, restores the expression and function of EZH2, and partially rescues hematopoietic defects and cellular properties. Our study demonstrates that ASO pharmacology is an actionable strategy for clinical development, challenging the existing paradigms in SF-mutated cancers.

In vitro assays demonstrated that PBs upregulated ESR1 and EZH2, induced DNA damage in normal breast epithelial cells, and enhanced proliferation and migration in breast cancer cells-effects reversed by ESR1 and EZH2 inhibitors. Together, these findings suggest that PBs may affect pathways relevant to breast cancer progression and act as potential environmental contributors.

The anti-tumor activity of NCTD is associated with the downregulation of EZH2 protein expression and concomitant inhibition of the JAK2/STAT3 signaling pathway. These findings provide novel insights into the molecular mechanisms underlying NCTD's anti-tumor activity.

Treatment with second-generation androgen receptor (AR) inhibitors, such as enzalutamide, can trigger lineage plasticity, promoting the transdifferentiation of PCa cells into an AR-independent, poorly differentiated neuroendocrine phenotype (NEPC)...Conclusions. These findings establish HOC as a multifaceted therapeutic entity capable of disrupting key NEPC oncogenic networks, highlighting its potential as a novel lead intervention for aggressive NEPC.