Glycolysis-induced drug resistance in tumors—A response to danger signals?

Marcucci, Fabrizio; Rumio, Cristiano

doi:10.1016/j.neo.2020.12.009

Cited by 67 publications

(52 citation statements)

References 163 publications

(222 reference statements)

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“…Hsa_circ_0085131 and hsa_circ_0092276 serve as competitive endogenous RNAs (ceRNAs) to elevate autophagy-associated factor ATG7 expression, thus enhancing CDDP resistance in NSCLC and doxorubicin (DOX) resistance in breast cancer ( 46 , 47 ). Tumor cells often switch to glycolysis, even under aerobic conditions, and components of the glycolytic pathway, including transporters, enzymes, and metabolites, are involved in inducing drug resistance ( 48 ). Some circRNAs mediate chemotherapy resistance by modulating glycolysis in tumor cells.…”

Section: Mechanisms Of Drug Resistancementioning

confidence: 99%

The Role of Circular RNAs in the Drug Resistance of Cancers

et al. 2022

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Cancer is a major threat to human health and longevity. Chemotherapy is an effective approach to inhibit cancer cell proliferation, but a growing number of cancer patients are prone to develop resistance to various chemotherapeutics, including platinum, paclitaxel, adriamycin, and 5-fluorouracil, among others. Significant progress has been made in the research and development of chemotherapeutic drugs over the last few decades, including targeted therapy drugs and immune checkpoint inhibitors; however, drug resistance still severely limits the application and efficacy of these drugs in cancer treatment. Recently, emerging studies have emphasized the role of circular RNAs (circRNAs) in the proliferation, migration, invasion, and especially chemoresistance of cancer cells by regulating the expression of related miRNAs and targeted genes. In this review, we comprehensively summarized the potential roles and mechanisms of circRNAs in cancer drug resistance including the efflux of drugs, apoptosis, intervention with the TME (tumor microenvironment), autophagy, and dysfunction of DNA damage repair, among others. Furthermore, we highlighted the potential value of circRNAs as new therapeutic targets and prognostic biomarkers for cancer.

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Section: Mechanisms Of Drug Resistancementioning

confidence: 99%

The Role of Circular RNAs in the Drug Resistance of Cancers

et al. 2022

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“…Glycolysis is the major pathway of glucose metabolism occurring in the cytosol of the cells by which glucose is metabolized to pyruvate. Considering the aerobic and anaerobic conditions occurring in tumors and different organisms pyruvate transportation may follow two different pathways ( 36 , 40 ).…”

Section: Glucose Metabolismmentioning

confidence: 99%

“…Drug resistance is induced directly by one of the elements involved in the pathway (transporters, enzymes) or indirectly, through an overall increase of the glycolytic metabolism or both situations can occur? Marcucci F et al in a recent review show that both situations can be present, and the upregulation of an individual enzyme is associated with enhanced overall elevation of the glycolytic metabolism ( 40 ).…”

Section: Future Challenges In Glucose Metabolism and Breast Cancer Tr...mentioning

confidence: 99%

Tumor Glucose and Fatty Acid Metabolism in the Context of Anthracycline and Taxane-Based (Neo)Adjuvant Chemotherapy in Breast Carcinomas

et al. 2022

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Breast cancer is characterized by considerable metabolic diversity. A relatively high percentage of patients diagnosed with breast carcinoma do not respond to standard-of-care treatment, and alteration in metabolic pathways nowadays is considered one of the major mechanisms responsible for therapeutic resistance. Consequently, there is an emerging need to understand how metabolism shapes therapy response, therapy resistance and not ultimately to analyze the metabolic changes occurring after different treatment regimens. The most commonly applied neoadjuvant chemotherapy regimens in breast cancer contain an anthracycline (doxorubicin or epirubicin) in combination or sequentially administered with taxanes (paclitaxel or docetaxel). Despite several efforts, drug resistance is still frequent in many types of breast cancer, decreasing patients’ survival. Understanding how tumor cells rapidly rewire their signaling pathways to persist after neoadjuvant cancer treatment have to be analyzed in detail and in a more complex system to enable scientists to design novel treatment strategies that target different aspects of tumor cells and tumor resistance. Tumor heterogeneity, the rapidly changing environmental context, differences in nutrient use among different cell types, the cooperative or competitive relationships between cells pose additional challenges in profound analyzes of metabolic changes in different breast carcinoma subtypes and treatment protocols. Delineating the contribution of metabolic pathways to tumor differentiation, progression, and resistance to different drugs is also the focus of research. The present review discusses the changes in glucose and fatty acid pathways associated with the most frequently applied chemotherapeutic drugs in breast cancer, as well the underlying molecular mechanisms and corresponding novel therapeutic strategies.

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“…Glycolytic TMR has been identified as one of the primary culprits in high-grade glioma (HGG) chemoresistance [ 96 , 97 ] and radioresistance [ 53 , 98 , 99 ]. Furthermore, TMR with a glycolytic preference instills a “domino effect” by mediating the aggregation of various glycolytic and chemoresistance activators (VEGF, IL-1β, IL-8, IL-6, TGF-β, and lactate) within the tumor stroma [ 100 , 101 ]. Cancerous cells employ glycolysis as a metabolic adaptation to meet the constant demand for cellular building blocks required for continuous and uncontrolled proliferation.…”

Section: Pfkfb3 Regulatory Mechanismsmentioning

confidence: 99%

Canonical and Non-Canonical Roles of PFKFB3 in Brain Tumors

Alvarez

Mandal

Chittiboina

2021

Cells

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PFKFB3 is a bifunctional enzyme that modulates and maintains the intracellular concentrations of fructose-2,6-bisphosphate (F2,6-P2), essentially controlling the rate of glycolysis. PFKFB3 is a known activator of glycolytic rewiring in neoplastic cells, including central nervous system (CNS) neoplastic cells. The pathologic regulation of PFKFB3 is invoked via various microenvironmental stimuli and oncogenic signals. Hypoxia is a primary inducer of PFKFB3 transcription via HIF-1alpha. In addition, translational modifications of PFKFB3 are driven by various intracellular signaling pathways that allow PFKFB3 to respond to varying stimuli. PFKFB3 synthesizes F2,6P2 through the phosphorylation of F6P with a donated PO4 group from ATP and has the highest kinase activity of all PFKFB isoenzymes. The intracellular concentration of F2,6P2 in cancers is maintained primarily by PFKFB3 allowing cancer cells to evade glycolytic suppression. PFKFB3 is a primary enzyme responsible for glycolytic tumor metabolic reprogramming. PFKFB3 protein levels are significantly higher in high-grade glioma than in non-pathologic brain tissue or lower grade gliomas, but without relative upregulation of transcript levels. High PFKFB3 expression is linked to poor survival in brain tumors. Solitary or concomitant PFKFB3 inhibition has additionally shown great potential in restoring chemosensitivity and radiosensitivity in treatment-resistant brain tumors. An improved understanding of canonical and non-canonical functions of PFKFB3 could allow for the development of effective combinatorial targeted therapies for brain tumors.

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Glycolysis-induced drug resistance in tumors—A response to danger signals?

Cited by 67 publications

References 163 publications

The Role of Circular RNAs in the Drug Resistance of Cancers

The Role of Circular RNAs in the Drug Resistance of Cancers

Tumor Glucose and Fatty Acid Metabolism in the Context of Anthracycline and Taxane-Based (Neo)Adjuvant Chemotherapy in Breast Carcinomas

Canonical and Non-Canonical Roles of PFKFB3 in Brain Tumors

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