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Flavonoids against the Warburg phenotype-concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism.

ABSTRACT: The Warburg effect is characterised by increased glucose uptake and lactate secretion in cancer cells resulting from metabolic transformation in tumour tissue. The corresponding molecular pathways switch from oxidative phosphorylation to aerobic glycolysis, due to changes in glucose degradation mechanisms known as the 'Warburg reprogramming' of cancer cells. Key glycolytic enzymes, glucose transporters and transcription factors involved in the Warburg transformation are frequently dysregulated during carcinogenesis considered as promising diagnostic and prognostic markers as well as treatment targets. Flavonoids are molecules with pleiotropic activities. The metabolism-regulating anticancer effects of flavonoids are broadly demonstrated in preclinical studies. Flavonoids modulate key pathways involved in the Warburg phenotype including but not limited to PKM2, HK2, GLUT1 and HIF-1. The corresponding molecular mechanisms and clinical relevance of 'anti-Warburg' effects of flavonoids are discussed in this review article. The most prominent examples are provided for the potential application of targeted 'anti-Warburg' measures in cancer management. Individualised profiling and patient stratification are presented as powerful tools for implementing targeted 'anti-Warburg' measures in the context of predictive, preventive and personalised medicine.

SUBMITTER: Samec M

PROVIDER: S-EPMC7429635 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Flavonoids against the Warburg phenotype-concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism.

Samec Marek M Liskova Alena A Koklesova Lenka L Samuel Samson Mathews SM Zhai Kevin K Buhrmann Constanze C Varghese Elizabeth E Abotaleb Mariam M Qaradakhi Tawar T Zulli Anthony A Kello Martin M Mojzis Jan J Zubor Pavol P Kwon Taeg Kyu TK Shakibaei Mehdi M Büsselberg Dietrich D Sarria Gustavo R GR Golubnitschaja Olga O Kubatka Peter P

The EPMA journal 20200730 3

The Warburg effect is characterised by increased glucose uptake and lactate secretion in cancer cells resulting from metabolic transformation in tumour tissue. The corresponding molecular pathways switch from oxidative phosphorylation to aerobic glycolysis, due to changes in glucose degradation mechanisms known as the 'Warburg reprogramming' of cancer cells. Key glycolytic enzymes, glucose transporters and transcription factors involved in the Warburg transformation are frequently dysregulated d ...[more]

PMID: 32843908

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Project description:BackgroundRecognising the early signs of ischemic stroke (IS) in emergency settings has been challenging. Machine learning (ML), a robust tool for predictive, preventive and personalised medicine (PPPM/3PM), presents a possible solution for this issue and produces accurate predictions for real-time data processing.MethodsThis investigation evaluated 4999 IS patients among a total of 10,476 adults included in the initial dataset, and 1076 IS subjects among 3935 participants in the external validation dataset. Six ML-based models for the prediction of IS were trained on the initial dataset of 10,476 participants (split participants into a training set [80%] and an internal validation set [20%]). Selected clinical laboratory features routinely assessed at admission were used to inform the models. Model performance was mainly evaluated by the area under the receiver operating characteristic (AUC) curve. Additional techniques-permutation feature importance (PFI), local interpretable model-agnostic explanations (LIME), and SHapley Additive exPlanations (SHAP)-were applied for explaining the black-box ML models.ResultsFifteen routine haematological and biochemical features were selected to establish ML-based models for the prediction of IS. The XGBoost-based model achieved the highest predictive performance, reaching AUCs of 0.91 (0.90-0.92) and 0.92 (0.91-0.93) in the internal and external datasets respectively. PFI globally revealed that demographic feature age, routine haematological parameters, haemoglobin and neutrophil count, and biochemical analytes total protein and high-density lipoprotein cholesterol were more influential on the model's prediction. LIME and SHAP showed similar local feature attribution explanations.ConclusionIn the context of PPPM/3PM, we used the selected predictors obtained from the results of common blood tests to develop and validate ML-based models for the diagnosis of IS. The XGBoost-based model offers the most accurate prediction. By incorporating the individualised patient profile, this prediction tool is simple and quick to administer. This is promising to support subjective decision making in resource-limited settings or primary care, thereby shortening the time window for the treatment, and improving outcomes after IS.Supplementary informationThe online version contains supplementary material available at 10.1007/s13167-022-00283-4.

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Flavonoids against the Warburg phenotype-concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism.

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Flavonoids against the Warburg phenotype-concepts of predictive, preventive and personalised medicine to cut the Gordian knot of cancer cell metabolism.

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