Targeting purine metabolism in ovarian cancer

Purine, an abundant substrate in organisms, is a critical raw material for cell proliferation and an important factor for immune regulation. The purine de novo pathway and salvage pathway are tightly regulated by multiple enzymes, and dysfunction in these enzymes leads to excessive cell proliferatio...

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Bibliographic Details
Published in:Journal of ovarian research 2022-08, Vol.15 (1), p.1-93, Article 93
Main Authors: Liu, Jingchun, Hong, Shasha, Yang, Jiang, Zhang, Xiaoyi, Wang, Ying, Wang, Haoyu, Peng, Jiaxin, Hong, Li
Format: Article
Language:English
Subjects:
6-Mercaptopurine
Adenosine
Adenosine deaminase
Adenosine kinase
Adenylate kinase
Antimetabolites
Apoptosis
Cancer therapies
CD73 antigen
Cell proliferation
Clopidogrel
Development and progression
Dihydrofolate reductase
Drug resistance
Editing
Enzymes
Fludarabine
Guanine
Health aspects
Homeostasis
Hypoxanthine
Immunoregulation
Inosine monophosphate
Lymphatic system
Lymphocytes
Medical prognosis
Metabolism
Metabolizing enzyme
Metastasis
Methotrexate
Methylenetetrahydrofolate reductase
Nucleosides
Ovarian cancer
Phosphoribosyltransferase
Phosphorylase
Physiological aspects
Purine metabolism
Purinergic signaling
Raw materials
Review
Thioguanine
Tumors
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Summary:Purine, an abundant substrate in organisms, is a critical raw material for cell proliferation and an important factor for immune regulation. The purine de novo pathway and salvage pathway are tightly regulated by multiple enzymes, and dysfunction in these enzymes leads to excessive cell proliferation and immune imbalance that result in tumor progression. Maintaining the homeostasis of purine pools is an effective way to control cell growth and tumor evolution, and exploiting purine metabolism to suppress tumors suggests interesting directions for future research. In this review, we describe the process of purine metabolism and summarize the role and potential therapeutic effects of the major purine-metabolizing enzymes in ovarian cancer, including CD39, CD73, adenosine deaminase, adenylate kinase, hypoxanthine guanine phosphoribosyltransferase, inosine monophosphate dehydrogenase, purine nucleoside phosphorylase, dihydrofolate reductase and 5,10-methylenetetrahydrofolate reductase. Purinergic signaling is also described. We then provide an overview of the application of purine antimetabolites, comprising 6-thioguanine, 6-mercaptopurine, methotrexate, fludarabine and clopidogrel. Finally, we discuss the current challenges and future opportunities for targeting purine metabolism in the treatment-relevant cellular mechanisms of ovarian cancer. Graphical Keywords: Purine metabolism, Ovarian cancer, Metabolizing enzyme, Antimetabolites, Purinergic signaling
ISSN:1757-2215
1757-2215
DOI:10.1186/s13048-022-01022-z