Marek Samec 1 , Alena Liskova 1 , Lenka Koklesova 1 , Samson Mathews Samuel 2 , Kevin Zhai 2 , Constanze Buhrmann 3 , Elizabeth Varghese 2 , Mariam Abotaleb 2 , Tawar Qaradakhi 4 , Anthony Zulli 4 , Martin Kello 5 , Jan Mojzis 5 , Pavol Zubor 6 , 7 , Taeg Kyu Kwon 8 , Mehdi Shakibaei 3 , Dietrich Büsselberg 2 , Gustavo R. Sarria 9 , Olga Golubnitschaja , 10 , Peter Kubatka , 11
30 July 2020
Predictive preventive personalised medicine (PPPM / 3PM), Cancer, Warburg phenotype, Flavonoids, Anticancer effect, Cell metabolism, Co-morbidities, Malignancy, Disease manifestation, Age, Patient stratification, Aggressive metastatic disease, Multi-omics, Biomarker patterns, Liquid biopsy, Modifiable risk factors, Risk assessment, Microcirculation, Systemic hypoxia, Ischemic lesions, Prognosis, Individualised patient profiles, Treatment algorithms, Liver malignancy, Triple-negative breast cancer, Prostate cancer, Pregnancy, Chemoresistance, Radioresistance, Glucose metabolism, Oxidative phosphorylation, Proliferation, Metabolic reprogramming, Positron emission tomography, Magnetic resonance spectroscopy, Tumour imaging, FDG-PET, Glucose intake, PET-CT, Individual outcome, Palliative medicine, Polyphenols, Glycolysis, Carcinogenesis, Prognostic markers, Aerobic glycolysis, Glycolytic inhibitors, Pleiotropic activity, HIF-1
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.