RT Journal Article
T1 The role of glycolysis in tumorigenesis: from biological aspects to therapeutic opportunities
A1 Cordani, Marco
A1 Michetti, Federica
A1 Zarrabi, Ali
A1 Zarepour, Atefeh
A1 Rumio, Cristiano
A1 Strippoli, Raffaele
A1 Marcucci, Fabrizio
AB 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.
PB Elsevier
SN 1522-8002
YR 2024
FD 2024-10
LK https://hdl.handle.net/20.500.14352/111257
UL https://hdl.handle.net/20.500.14352/111257
LA eng
NO Cordani M, Michetti F, Zarrabi A, Zarepour A, Rumio C, Strippoli R, Marcucci F. The role of glycolysis in tumorigenesis: From biological aspects to therapeutic opportunities. Neoplasia 2024;58:101076. https://doi.org/10.1016/j.neo.2024.101076.
NO Fundings:MC was supported by grant RYC2021-031003I funded by MICIU/AEI/10.13039/501100011033 and by European Union NextGenerationEU/PRTR; RS was supported by a research grant from the Italian ministry of University and Research (MIUR) P2022XZKBM financed by the European Union NextGeneration and by a research grant IG 26394 from Associazione Italiana per la Ricerca sul Cancro (AIRC).
NO European Commission
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Ministero dell'Università e della Ricerca (Italia)
NO Associazione Italiana per la Ricerca sul Cancro
DS Docta Complutense
RD 17 abr 2025