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Benefits and Challenges of Inhibiting EZH2 in Malignant Pleural Mesothelioma
Mhd Ouis Al Khatib1,2, Giulia Pinton1, Laura Moro1
1Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro", 28100 Novara, Italy.
Abstract:
Malignant pleural mesothelioma (MPM) is an aggressive thoracic cancer that is mainly associated with prior exposure to asbestos fibers. Despite being a rare cancer, its global rate is increasing and the prognosis remains extremely poor. Over the last two decades, despite the constant research of new therapeutic options, the combination chemotherapy with cisplatin and pemetrexed has remained the only first-line therapy for MPM. The recent approval of immune checkpoint blockade (ICB)-based immunotherapy has opened new promising avenues of research. However, MPM is still a fatal cancer with no effective treatments. Enhancer of zeste homolog 2 (EZH2) is a histone methyl transferase that exerts pro-oncogenic and immunomodulatory activities in a variety of tumors. Accordingly, a growing number of studies indicate that EZH2 is also an oncogenic driver in MPM, but its effects on tumor microenvironments are still largely unexplored. This review describes the state-of-the-art of EZH2 in MPM biology and discusses its potential use both as a diagnostic and therapeutic target. We highlight current gaps of knowledge, the filling of which will likely favor the entry of EZH2 inhibitors within the treatment options for MPM patients.
Insights
Malignant pleural mesothelioma (MPM) remains a poor-prognosis cancer. This review explores Enhancer of zeste homolog 2 (EZH2) as a potential diagnostic and therapeutic target for MPM, offering new treatment avenues.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Malignant pleural mesothelioma (MPM) is an aggressive thoracic cancer linked to asbestos exposure with a poor prognosis.
- Current first-line chemotherapy (cisplatin and pemetrexed) and emerging immunotherapies offer limited efficacy for MPM.
- Enhancer of zeste homolog 2 (EZH2) is implicated in cancer but its role in MPM tumor microenvironments is understudied.
Purpose of the Study:
- To review the current understanding of EZH2 in MPM biology.
- To discuss the potential of EZH2 as a diagnostic and therapeutic target in MPM.
- To identify knowledge gaps crucial for developing EZH2 inhibitors for MPM treatment.
Main Methods:
- Literature review of EZH2's role in MPM.
- Analysis of EZH2's oncogenic and immunomodulatory functions.
- Discussion of EZH2 as a biomarker and therapeutic target.
Main Results:
- EZH2 acts as an oncogenic driver in MPM.
- EZH2 influences the tumor microenvironment in MPM.
- EZH2 presents potential as both a diagnostic marker and a therapeutic target.
Conclusions:
- Targeting EZH2 may offer novel therapeutic strategies for MPM.
- Further research into EZH2's functions is needed to optimize its clinical application.
- EZH2 inhibitors could become a valuable addition to MPM treatment options.
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