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.
Keywords: Aerobic glycolysis; Age; Aggressive metastatic disease; Anticancer effect; Biomarker patterns; Cancer; Carcinogenesis; Cell metabolism; Chemoresistance; Co-morbidities; Disease manifestation; FDG-PET; Flavonoids; Glucose intake; Glucose metabolism; Glycolysis; Glycolytic inhibitors; HIF-1; Individual outcome; Individualised patient profiles; Ischemic lesions; Liquid biopsy; Liver malignancy; Magnetic resonance spectroscopy; Malignancy; Metabolic reprogramming; Microcirculation; Modifiable risk factors; Multi-omics; Oxidative phosphorylation; PET-CT; Palliative medicine; Patient stratification; Pleiotropic activity; Polyphenols; Positron emission tomography; Predictive preventive personalised medicine (PPPM / 3PM); Pregnancy; Prognosis; Prognostic markers; Proliferation; Prostate cancer; Radioresistance; Risk assessment; Systemic hypoxia; Treatment algorithms; Triple-negative breast cancer; Tumour imaging; Warburg phenotype.
© The Author(s) 2020.