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The emerging roles of histone demethylases in cancers

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Abstract

Modulation of histone methylation status is regarded as an important mechanism of epigenetic regulation and has substantial clinical potential for the therapy of diseases, including cancer and other disorders. The present study aimed to provide a comprehensive introduction to the enzymology of histone demethylases, as well as their cancerous roles, molecular mechanisms, therapeutic possibilities, and challenges for targeting them, in order to advance drug design for clinical therapy and highlight new insight into the mechanisms of these enzymes in cancer. A series of clinical trials have been performed to explore potential roles of histone demethylases in several cancer types. Numerous targeted inhibitors associated with immunotherapy, chemotherapy, radiotherapy, and targeted therapy have been used to exert anticancer functions. Future studies should evaluate the dynamic transformation of histone demethylases leading to carcinogenesis and explore individual therapy.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

KDM:

Histone lysine demethylase

LSD1:

Lysine specific demethylase 1

JMJD:

JumonjiC domain-containing demethylase

PELP1:

Proline glutamic acid and leucine-rich protein 1

EZH2:

Zeste homolog 2

ER:

Estrogen receptor

CSC:

Cancer stem-cell

CRPC:

Castration-resistant prostate cancer

DNMT:

DNA methyltransferase

HIF:

Hypoxia-induced factor

EpCAM:

Epithelial cell adhesion molecule

VHL:

Von Hippel Lindau

ATRA:

All-trans-retinoic acid

MLL:

Mixed lineage leukemia

AML:

Acute myeloid leukemia

JAK:

Janus kinase

lncRNA:

Long noncoding RNA

BRCA:

Breast cancer susceptibility gene

HNSCC:

Head and neck squamous cell carcinoma

NEPC:

Neuroendocrine prostate cancer

PKM:

Pyruvate kinase muscle isozyme

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Funding

This work was supported by Chongqing Science and Technology Bureau (Basic and Frontier Research Project with grant no. cstc2018jcyjAX0645) and the Chongqing Municipal Health Committee (Science and Health Joint Medical Research Project with grant no. 2018QNXM041) by Dr. Dali Tong and National Nature Science Foundation of China (81902302) by Dr. Ying Tang.

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  1. Department of Urological Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, People’s Republic of China

    Dali Tong

  2. Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China

    Ying Tang

  3. Department of Pathology, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, People’s Republic of China

    Peng Zhong

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Dr. Dali Tong designed, wrote, and reviewed the MS. Dr. Ying Tang checked and participated in partial revision of the MS. Dr. Peng Zhong provided the literature reviewing and partial data collection of MS.

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Tong, D., Tang, Y. & Zhong, P. The emerging roles of histone demethylases in cancers. Cancer Metastasis Rev (2024). https://doi.org/10.1007/s10555-023-10160-9

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