One-carbon metabolism and nucleotide biosynthesis as attractive targets for anticancer therapy
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// Oleg Shuvalov 1 , Alexey Petukhov 1, 2 , Alexandra Daks 1 , Olga Fedorova 1 , Elena Vasileva 1 , Nickolai A. Barlev 1 1 Institute of Cytology RAS, Saint-Petersburg, Russian Federation 2 Institute of Hematology, Almazov Federal North-West Medical Research Centre, Saint-Petersburg, Russian Federation Correspondence to: Oleg Shuvalov, email: oleg8988@mail.ru Nickolai A. Barlev, email: nick.a.barlev@gmail.com Keywords: cancer metabolism, one-carbon metabolism, anti-cancer therapy, c-Myc, p53 Received: October 19, 2016 Accepted: December 02, 2016 Published: February 03, 2017 ABSTRACT Cancer-related metabolism has recently emerged as one of the “hallmarks of cancer”. It has several important features, including altered metabolism of glucose and glutamine. Importantly, altered cancer metabolism connects different biochemical pathways into the one fine-tuned metabolic network, which stimulates high proliferation rates and plasticity to malignant cells. Among the keystones of cancer metabolism are one-carbon metabolism and nucleotide biosynthesis, which provide building blocks to anabolic reactions. Accordingly, the importance of these metabolic pathways for anticancer therapy has well been documented by more than fifty years of clinical use of specific metabolic inhibitors – methotrexate and nucleotides analogs. In this review we discuss one-carbon metabolism and nucleotide biosynthesis as common and specific features of many, if not all, tumors. The key enzymes involved in these pathways also represent promising anti-cancer therapeutic targets. We review different aspects of these metabolic pathways including their biochemistry, compartmentalization and expression of the key enzymes and their regulation at different levels. We also discuss the effects of known inhibitors of these pathways as well as the recent data on other enzymes of the same pathways as perspective pharmacological targets.
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Metabolic reprogramming is a known hallmark of cancer cells, in which they manifest diverse metabolic phenotypes to maintain their proliferation and to combat anticancer therapies.
“Metabolic reprogramming is a known hallmark of cancer cells, in which they manifest diverse metabolic phenotypes to maintain their proliferation and to combat anticancer therapies (Shuvalov et al., 2017; Sun et al., 2020).”
From An Arthropod Hormone, Ecdysterone, Inhibits the Growth of Breast Cancer Cells via Different Mechanisms (2020) · cites this paper as Shuvalov et al., 2017
One-carbon metabolism supplies cancer cells with nucleotides, SAM, glutathione, some amino acids, etc.
“One-carbon metabolism supplies cancer cells with nucleotides, which limit cell divisions: SAM—the main donor of methyl groups; glutathione—an important factor of redox homeostasis; some amino acids; etc. [40,65].”
From 20-Hydroxyecdysone Confers Antioxidant and Antineoplastic Properties in Human Non-Small Cell Lung Cancer Cells (2023) · cites this paper as [65]
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Macropinocytosis confers resistance to therapies targeting cancer anabolism
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The metabolic landscape of lung cancer: New insights in a disturbed glucose metabolism
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Linking Metabolic Reprogramming, Plasticity and Tumor Progression
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Self-citationAlterations in the gastric microbiota and metabolites in gastric cancer: An update review
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Shuvalov, O., Kirdeeva, Y., Fefilova, E., Daks, A., Fedorova, O., Parfenyev, S., Nazarov, A., Vlasova, Y., Krasnov, G. S., & Barlev, N. A. (2024) · Antioxidants · doi:10.3390/antiox13111349 · Cited by 9 · see citing works
Self-citation
- Authors
- Shuvalov, O., Petukhov, A., Daks, A., Fedorova, O., Vasileva, E., & Barlev, N. A.
- Affiliations
- Institute of Cytology (RU)
- Federal Almazov North-West Medical Research Centre (RU)
- Corresponding author
- Barlev, Nickolai A.
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2017-02-03
- Volume
- 8
- Issue
- 14
- Pages
- 23955-23977
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC5410357
- OpenAlex
- W2585195223
- Cited by
- 168
- References
- 177
- Citations by year
- 2026: 18 · 2025: 22 · 2024: 20 · 2023: 14 · 2022: 22 · 2021: 24 · 2020: 22 · 2019: 13 · 2018: 11 · 2017: 2
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Russian Foundation for Basic Research (14-50-00068, 16-34-60228)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Keywords
- one-carbon metabolism, nucleotide synthesis, cancer metabolism, anticancer drug targets, methotrexate, nucleotide analogues, c-Myc, p53, metabolic inhibitors, metabolic enzymes
- MeSH terms
- Animals, Carbon, Humans, Neoplasms, Nucleotides, Metabolic Networks and Pathways, Molecular Targeted Therapy
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