Open access

Histone deacetylase activity limits the response to EZH2 inhibition-based therapy in epithelioid sarcoma and is targetable by epigenetic combination

N. Arrighetti C. Soffientini V. Zuco Stefano Percio L. Cleris Suzan Abdulrazak Ahmed Elisa Del Savio L. Sigalotti R. Maestro S. Brich G. P. Dagrada M. Barisella P. Collini A. Kentsis Paul H. Huang A. Gronchi A. Frezza S. Stacchiotti Nadia Zaffaroni Sandro Pasquali

Aug 2026 · bioRxiv · 1 citation · 55 references

Biology

TL;DR

Findings identify failure to accumulate H3K27 acetylation as a hallmark of resistance to EZH2 inhibition-based treatment, and show that pharmacological HDAC inhibition can restore this chromatin transition and re-sensitize resistant tumors, providing a rationale for combined epigenetic targeting strategies in INI1-deficient malignancies.

DOI Semantic Scholar

Read PDF

Similar papers

Open access Sep 2026

Dual DNMT–EZH2 Inhibition as a Stroma-Directed Strategy in Castration-Resistant Prostate Cancer: A Commentary

Background: Castration-resistant prostate cancer (CRPC) remains a lethal progression state despite androgen-deprivation therapy, driven by epigenetic plasticity and a fibrotic tumour microenvironment. Single-agent epigenetic inhibitors have limited activity in solid tumours, partly because compensatory H3K27me3-mediate...

Rong-Xin Chang, Guo-Dong Liu · Serican Journal of Medicine · 0 citations

Open access Oct 2026

EZH2 Inhibition Induces a Metabolic Stress Response Sensitizing Triple-Negative Breast Cancer to Glutaminase Targeting.

EZH2, the catalytic subunit of the histone methyltransferase complex PRC2, is overexpressed and associated with poor prognosis in triple-negative breast cancer (TNBC). Although EZH2 inhibition significantly alters chromatin landscapes and gene expression, it has limited impact on the growth of TNBC models, suggesting a...

Lucas Porras, M. Carrière, Ann-Sophie Gironne et al. · Cancer Research · 0 citations

Review Open access Aug 2026

Enhancer of Zeste Homolog 2 (EZH2): From Glioblastoma Biology to Potential Epigenetic Therapy

Although EZH2 expression is not consistently associated with overall survival in GBM, EZH2 remains a promising therapeutic target due to its roles in stemness and treatment resistance and its complex functions and therapeutic potential.

J. Grzegorzewski, M. Lindner, Dagmara Lisińska et al. · International Journal of Mol... · 0 citations

Open access Aug 2026

KAT8‐Low Osteosarcoma Suppresses Cisplatin Sensitivity via H4K16ac‐Mediated Cell Apoptosis

The hypothesis emphasizes the need to clarify the molecular mechanisms and signaling pathways associated with KAT8–H4K16ac, especially in relation to apoptotic pathways, which could offer new insights and justifications for treatment strategies in cisplatin‐resistant osteosarcoma.

Zhen-Qun Zhao, Guohui Yu, Shi-Kui Wu et al. · Med Research · 0 citations

Open access Sep 2026

KDM1A/HDAC2-driven epigenetic dysregulation maintains a drug-resistant, relapse-initiating glioblastoma cell niche at the peri-tumoral margin.

It is indicated that MPT0G521 disrupts the G2/M activation and mitotic machinery, thereby suppressing proliferative and resistant GBM subpopulations and holding strong promise for overcoming GBM heterogeneity and reducing recurrence.

An-Chih Wu, J. Chuang, Jr-Jiun Liu et al. · Biochemical Pharmacology · 0 citations

Review Open access Sep 2026

Molecular reprogramming in cutaneous melanoma: the central role of G9a and EZH2 methyltransferase inhibitors in tumor plasticity, immune evasion, and therapeutic resistance

Cutaneous melanoma remains a leading cause of skin cancer-related mortality despite significant therapeutic advances, with treatment resistance and immune evasion representing major clinical challenges. Epigenetic dysregulation, particularly through the histone methyltransferases G9a (EHMT2) and Enhancer of Zeste Homol...

Melissa Yoshimi Sakamoto Maeda Nisimoto, Daniel Arcuschin de Oliveira, Heitor Raia Bottura et al. · Frontiers in Pharmacology · 0 citations