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Cited by 40Cancer, Hypoxia, and MetabolismMetabolism, Diabetes, and CancerCancer and biochemical research

The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities

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Cordani, Marco, Michetti, Federica, Zarrabi, Ali, Zarepour, Atefeh, Rumio, Cristiano, Strippoli, Raffaele, Marcucci, Fabrizio·2024·Neoplasia
DOI 10.1016/j.neo.2024.101076PMC PMC11555605
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Abstract

Glycolytic metabolism generates energy and intermediates for biomass production. Tumor-associated glycolysis is upregulated compared to normal tissues in response to tumor cell-autonomous or non-autonomous stimuli. The consequences of this upregulation are twofold. First, the metabolic effects of glycolysis become predominant over those mediated by oxidative metabolism. Second, overexpressed components of the glycolytic pathway (i.e. enzymes or metabolites) acquire new functions unrelated to their metabolic effects and which are referred to as "moonlighting" functions. These functions include induction of mutations and other tumor-initiating events, effects on cancer stem cells, induction of increased expression and/or activity of oncoproteins, epigenetic and transcriptional modifications, bypassing of senescence and induction of proliferation, promotion of DNA damage repair and prevention of DNA damage, antiapoptotic effects, inhibition of drug influx or increase of drug efflux. Upregulated metabolic functions and acquisition of new, non-metabolic functions lead to biological effects that support tumorigenesis: promotion of tumor initiation, stimulation of tumor cell proliferation and primary tumor growth, induction of epithelial-mesenchymal transition, autophagy and metastasis, immunosuppressive effects, induction of drug resistance and effects on tumor accessory cells. These effects have negative consequences on the prognosis of tumor patients. On these grounds, it does not come to surprise that tumor-associated glycolysis has become a target of interest in antitumor drug discovery. So far, however, clinical results with glycolysis inhibitors have fallen short of expectations. In this review we propose approaches that may allow to bypass some of the difficulties that have been encountered so far with the therapeutic use of glycolysis inhibitors.

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Authors
Cordani, M., Michetti, F., Zarrabi, A., Zarepour, A., Rumio, C., Strippoli, R., & Marcucci, F.
Affiliations
  • Universidad Complutense de Madrid (ES)
  • Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani (IT)
  • Istinye University (TR)
  • Saveetha University (IN)
  • University of Milan (IT)
Corresponding author
  • Strippoli, Raffaele
  • Marcucci, Fabrizio
ORCID
Venue
Neoplasia
Publisher
Elsevier BV
Published
2024-12
Volume
58
Pages
101076
ISSN
1476-5586 (ISSN-L)
DOI
10.1016/j.neo.2024.101076
PMC
PMC11555605
OpenAlex
W4403904871
Cited by
40
References
306
Citations by year
2026: 18 · 2025: 22
FWCI
1.95
Type
journal article
Language
en
Open access
Licence
Locations
  • Neoplasia (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion, cc-by-nc-nd)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • European Commission (10.13039/501100011033, 13039/501100011033, 501100011033, /AEI/10.13039/501100011033, P2022XZKBM)
  • Ministero dell’Istruzione, dell’Università e della Ricerca (AEI/10.13039/501100011033, P2022XZKBM)
  • Associazione Italiana per la Ricerca sul Cancro
  • Agencia Estatal de Investigación (AEI//10.13039/501100011033/, RYC2021-031003I, 501100011033, 10.13039/501100011033, 13039, .13039/501100011033, 10.13039, AEI/10)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
Keywords
glycolysis, carcinogenesis, moonlighting function, cancer metabolism, cancer stem cells, drug resistance, epithelial-mesenchymal transition, metastasis, immunosuppression, glycolysis inhibitors, anticancer drug discovery, DNA repair, epigenetic modifications, tumor microenvironment
MeSH terms
Animals, Antineoplastic Agents, Cell Transformation, Neoplastic, Glycolysis, Humans, Neoplasms, Neoplastic Stem Cells, Carcinogenesis

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