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Review Article | Open Access

MDM2 inhibitors in cancer immunotherapy: Current status and perspective

Qinru Zenga,b,1Shaocheng Zenga,b,1Xiaofeng Daia,b,1Yun Dinga,bChunye Huanga,bRuiwen Ruana,bJianping Xionga,bXiaomei Tangc( )Jun Denga,b,d( )
Department of Oncology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, China
Jiangxi Key Laboratory for Individual Cancer Therapy, Nanchang, Jiangxi 330006, China
Department of Oncology, Jiangxi Chest Hospital, Nanchang, Jiangxi 330006, China
Postdoctoral Innovation Practice Base, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China

1 These authors contributed equally to this work.

Peer review under responsibility of Chongqing Medical University.

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Abstract

Murine double minute 2 (MDM2) plays an essential role in the cell cycle, apoptosis, DNA repair, and oncogene activation through p53-dependent and p53-independent signaling pathways. Several preclinical studies have shown that MDM2 is involved in tumor immune evasion. Therefore, MDM2-based regulation of tumor cell-intrinsic immunoregulation and the immune microenvironment has attracted increasing research attention. In recent years, immune checkpoint inhibitors targeting PD-1/PD-L1 have been widely used in the clinic. However, the effectiveness of a single agent is only approximately 20%–40%, which may be related to primary and secondary drug resistance caused by the dysregulation of oncoproteins. Here, we reviewed the role of MDM2 in regulating the immune microenvironment, tumor immune evasion, and hyperprogression during immunotherapy. In addition, we summarized preclinical and clinical findings on the use of MDM2 inhibitors in combination with immunotherapy in tumors with MDM2 overexpression or amplification. The results reveal that the inhibition of MDM2 could be a promising strategy for enhancing immunotherapy.

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Genes & Diseases
Article number: 101279
Cite this article:
Zeng Q, Zeng S, Dai X, et al. MDM2 inhibitors in cancer immunotherapy: Current status and perspective. Genes & Diseases, 2024, 11(6): 101279. https://doi.org/10.1016/j.gendis.2024.101279

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Received: 30 October 2023
Revised: 13 February 2024
Accepted: 21 February 2024
Published: 28 March 2024
© 2024 The Authors.

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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