New perspective on epigenetic modification and immunotherapy in endometrial cancer.
7 affiliations
- 1Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
- 2Zhengzhou Key Laboratory of Cervical Disease, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
- 3National Clinical Research Center for Obstetrics and Gynecology, Henan Branch, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
- 4The Second Clinical Medical School of Zhengzhou University, Zhengzhou, China.
- 5Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China. [email protected].
- 6Zhengzhou Key Laboratory of Cervical Disease, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China. [email protected].
- 7National Clinical Research Center for Obstetrics and Gynecology, Henan Branch, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China. [email protected].
Abstract
Endometrial carcinoma (EC) is a heterogeneous gynecological malignancy. Epigenetic dysregulation promotes the initiation, progression, immune evasion, and therapeutic resistance of EC. Aberrant DNA methylation, histone methylation, histone acetylation, and chromatin remodeling affect key EC-associated pathways and help shape distinct molecular subtypes, including POLE-mutated and mismatch repair-deficient tumours. In this review, we summarize the major epigenetic alterations implicated in EC, with emphasis on DNA methylation regulators, histone-modifying enzymes, and emerging epigenetic targets such as DNMTs, HDACs, LSD1, EZH2, PRMTs, and BET proteins. We further highlight the rapidly evolving immunotherapy landscape in EC, including clinically established or practice-changing regimens such as pembrolizumab-, dostarlimab-, durvalumab-, and lenvatinib-based strategies, particularly in advanced or recurrent disease. In parallel, we discuss investigational epigenetic therapies, including DNMT inhibitors, HDAC inhibitors, LSD1 inhibitors, EZH2-targeted agents, PRMT inhibitors, and BRD4-directed approaches, which are being explored to restore tumour suppressor pathways, enhance tumour immunogenicity, and improve sensitivity to immune checkpoint blockade. By integrating EC-specific epigenetic mechanisms with current immunotherapy advances and ongoing combination strategies, this review provides a clinically oriented perspective on biomarker-guided precision treatment for EC.
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BibTeX
@article{zhang2026perspective,
title = {{New perspective on epigenetic modification and immunotherapy in endometrial cancer.}},
author = {Haoqian Zhang and Dandan Shen and Nanshan Lin and Li Yang and Chenchen Ren},
journal = {Clinical epigenetics},
year = {2026},
month = jul,
doi = {10.1186/s13148-026-02174-1},
url = {https://europepmc.org/article/MED/42894251},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - New perspective on epigenetic modification and immunotherapy in endometrial cancer.
AU - Haoqian Zhang
AU - Dandan Shen
AU - Nanshan Lin
AU - Li Yang
AU - Chenchen Ren
PY - 2026
DA - 2026/07/01
JO - Clinical epigenetics
DO - 10.1186/s13148-026-02174-1
UR - https://europepmc.org/article/MED/42894251
AB - Endometrial carcinoma (EC) is a heterogeneous gynecological malignancy. Epigenetic dysregulation promotes the initiation, progression, immune evasion, and therapeutic resistance of EC. Aberrant DNA methylation, histone methylation, histone acetylation, and chromatin remodeling affect key EC-associated pathways and help shape distinct molecular subtypes, including POLE-mutated and mismatch repair-deficient tumours. In this review, we summarize the major epigenetic alterations implicated in EC, with emphasis on DNA methylation regulators, histone-modifying enzymes, and emerging epigenetic targets such as DNMTs, HDACs, LSD1, EZH2, PRMTs, and BET proteins. We further highlight the rapidly evolving immunotherapy landscape in EC, including clinically established or practice-changing regimens such as pembrolizumab-, dostarlimab-, durvalumab-, and lenvatinib-based strategies, particularly in advanced or recurrent disease. In parallel, we discuss investigational epigenetic therapies, including DNMT inhibitors, HDAC inhibitors, LSD1 inhibitors, EZH2-targeted agents, PRMT inhibitors, and BRD4-directed approaches, which are being explored to restore tumour suppressor pathways, enhance tumour immunogenicity, and improve sensitivity to immune checkpoint blockade. By integrating EC-specific epigenetic mechanisms with current immunotherapy advances and ongoing combination strategies, this review provides a clinically oriented perspective on biomarker-guided precision treatment for EC.
SN - 1868-7083
ER -