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Combining EZH2 inhibitors with other therapies for solid tumors: more choices for better effects

    Rong Huang‡

    The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, China

    ‡Authors contributed equally

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    ,
    Yirong Wu‡

    The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, China

    ‡Authors contributed equally

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    &
    Zhengyun Zou

    *Author for correspondence:

    E-mail Address: zouzhengyun@njglyy.com

    The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road, Nanjing, 210008, China

    Published Online:https://doi.org/10.2217/epi-2022-0320

    EZH2 is an epigenetic regulator that methylates lysine 27 on histone H3 (H3K27) and is closely related to the development and metastasis of tumors. It often shows gain-of-function mutations in hematological tumors, while it is often overexpressed in solid tumors. EZH2 inhibitors have shown good efficacy in hematological tumors in clinical trials but poor efficacy in solid tumors. Therefore, current research on EZH2 inhibitors has focused on exploring additional combination strategies in solid tumors. Herein we summarize the combinations and mechanisms of EZH2 inhibitors and other therapies, including immunotherapy, targeted therapy, chemotherapy, radiotherapy, hormone therapy and epigenetic therapy, both in clinical trials and preclinical studies, aiming to provide a reference for better antitumor effects.

    Plain language summary

    EZH2 is a histone methyltransferase whose high expression is associated with a poor prognosis in various solid tumors. It is considered a target for cancer treatment. However, EZH2 inhibitors as monotherapy have shown disappointing efficacy in most solid tumors. This review summarizes the strategies of combining EZH2 inhibitors with other treatment regimens and their associated molecular mechanisms.

    Tweetable abstract

    Review describing EZH2 inhibitors combined with other antitumor therapy to provide therapeutic synergy for solid tumor treatment.

    Papers of special note have been highlighted as: • of interest

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