(Press-News.org) The critical role of EZH2, an essential epigenetic regulator, in cancer progression and treatment is underscored in this new review article published in Genes & Diseases. The study highlights the transformative potential of EZH2 inhibition, paving the way for a new generation of targeted therapies aimed at disrupting tumor growth and overcoming treatment resistance.
EZH2, a core component of the Polycomb Repressive Complex 2 (PRC2), plays a fundamental role in silencing tumor suppressor genes through histone methylation. Its overexpression has been implicated in a variety of malignancies, including breast cancer, prostate cancer, glioblastoma, and lymphoma. The ability of EZH2 inhibitors to reverse these effects represents a major advance in cancer therapy, offering new hope for patients with aggressive and treatment-resistant tumors.
Inhibition of EZH2 disrupts key signaling pathways that drive tumor proliferation, invasion, and survival. Beyond its canonical role in H3K27 trimethylation, EZH2 has been found to regulate non-histone proteins, activating pathways that promote metastasis and chemotherapy resistance. By targeting EZH2, researchers aim to counteract these mechanisms, restoring the expression of tumor suppressor genes and sensitizing cancer cells to conventional treatments.
The first FDA-approved EZH2 inhibitor, tazemetostat, has already demonstrated significant clinical benefits in epithelioid sarcoma and follicular lymphoma, marking an important milestone in the development of epigenetic-based cancer treatments. Ongoing research is expanding the scope of EZH2-targeting strategies, including combination therapies that integrate immune checkpoint inhibitors, chemotherapy, and radiation therapy. These approaches aim to enhance treatment efficacy, reduce drug resistance, and improve long-term survival rates.
Despite the promise of EZH2 inhibitors, challenges remain in optimizing their use. Tumor heterogeneity, adaptive resistance mechanisms, and potential off-target effects highlight the need for further investigation into the precise role of EZH2 in different cancer types. Advanced biomarker studies are being pursued to identify predictive indicators that can guide patient selection and personalized treatment approaches.
The growing body of evidence supporting EZH2 as a therapeutic target is revolutionizing the field of oncology, offering a powerful tool for combating some of the most aggressive and treatment-resistant cancers.
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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
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Impact Factor: 6.9
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Reference
Mengfei Xu, Chunyan Xu, Rui Wang, Qing Tang, Qichun Zhou, Wanyin Wu, Xinliang Wan, Handan Mo, Jun Pan, Sumei Wang, Treating human cancer by targeting EZH2, Genes & Diseases, Volume 12, Issue 3, 2025, 101313, https://doi.org/10.1016/j.gendis.2024.101313
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