Glycolysis-induced drug resistance in tumors—A response to danger signals?
| Autor: | Cristiano Rumio, Fabrizio Marcucci |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
PFKFB3 PFKFB isoform 3 Cancer Research GAPDH glyceraldehyde 3-phosphate dehydrogenase OXPHOS oxidative phosphorylation ATG autophagy related Apoptosis Drug resistance Review Article TKI tyrosine kinase inhibitor Oxidative Phosphorylation 0302 clinical medicine Neoplasms Glycolysis NADPH nicotinamide adenine dinucleotide phosphate reduced media_common LDH lactate dehydrogenase Chemistry ABC ATP-binding cassette mTOR mechanistic target of rapamycin EMT TME tumor microenvironment PFKFB phosphofructo-2-kinase/fructose-2 6-biphosphatase lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell biology GLUT glucose transporter Mitochondria HIF hypoxia-inducible factor PGK1 PGK isoform 1 ENO enolase 030220 oncology & carcinogenesis Efflux EMT epithelial-mesenchymal transition PI3K phosphoinositide 3-kinase Drug PDK1 PDK isoform 1 ATP adenosine triphosphate Epithelial-Mesenchymal Transition media_common.quotation_subject DDR DNA damage repair HK2 HK isoform 2 PPP pentose phosphate pathway Antineoplastic Agents lcsh:RC254-282 03 medical and health sciences ROS reactive oxygen species Cell Line Tumor PGK phosphoglycerate kinase PFKP PFK platelet type Animals Humans LDHA LDH isoform A mAb monoclonal antibody Tumors Tumor microenvironment Innate immune system Autophagy Danger HK hexokinase PDH pyruvate dehydrogenase EGFR epidermal growth factor receptor Metabolic pathway 030104 developmental biology Glucose Drug Resistance Neoplasm PK pyruvate kinase PKM2 PK isoform M2 ALDO fructose biphosphate aldolase ENO1 ENO isoform 1 Energy Metabolism PDK pyruvate dehydrogenase kinase |
| Zdroj: | Neoplasia (New York, N.Y.) Neoplasia: An International Journal for Oncology Research, Vol 23, Iss 2, Pp 234-245 (2021) |
| ISSN: | 1476-5586 1522-8002 |
| Popis: | Tumor cells often switch from mitochondrial oxidative metabolism to glycolytic metabolism even under aerobic conditions. Tumor cell glycolysis is accompanied by several nonenzymatic activities among which induction of drug resistance has important therapeutic implications. In this article, we review the main aspects of glycolysis-induced drug resistance. We discuss the classes of antitumor drugs that are affected and the components of the glycolytic pathway (transporters, enzymes, metabolites) that are involved in the induction of drug resistance. Glycolysis-associated drug resistance occurs in response to stimuli, either cell-autonomous (e.g., oncoproteins) or deriving from the tumor microenvironment (e.g., hypoxia or pseudohypoxia, mechanical cues, etc.). Several mechanisms mediate the induction of drug resistance in response to glycolytic metabolism: inhibition of apoptosis, induction of epithelial-mesenchymal transition, induction of autophagy, inhibition of drug influx and increase of drug efflux. We suggest that drug resistance in response to glycolysis comes into play in presence of qualitative (e.g., expression of embryonic enzyme isoforms, post-translational enzyme modifications) or quantitative (e.g., overexpression of enzymes or overproduction of metabolites) alterations of glycolytic metabolism. We also discern similarities between changes occurring in tumor cells in response to stimuli inducing glycolysis-associated drug resistance and those occurring in cells of the innate immune system in response to danger signals and that have been referred to as danger-associated metabolic modifications. Eventually, we briefly address that also mitochondrial oxidative metabolism may induce drug resistance and discuss the therapeutic implications deriving from the fact that the main energy-generating metabolic pathways may be both at the origin of antitumor drug resistance. |
| Databáze: | OpenAIRE |
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