Energy metabolism as the hub of advanced non-small cell lung cancer management: a comprehensive view in the framework of predictive, preventive, and personalized medicine

• Published in: The EPMA journal 2024-04, Vol.15 (2), p.289-319
• Main Authors: Bajinka, Ousman, Ouedraogo, Serge Yannick, Golubnitschaja, Olga, Li, Na, Zhan, Xianquan
• Format: Article
• Language: English
• Subjects: Apoptosis; Auranofin; Biomedical and Life Sciences; Biomedicine; Cancer; Care and treatment; Development and progression; Disease; DNA methylation; Drug development; Endothelin; Energy; Health risk assessment; Health risks; Homeostasis; Immunotherapy; Lung cancer; Lung cancer, Non-small cell; Lung cancer, Small cell; Medical care, Cost of; Medical policy; Medical research; Medicine, Experimental; Medicine/Public Health; Metabolism; Metabolites; Metastasis; Methylation; Physiological aspects; Precision medicine; Prevention; Review; Risk assessment
• ISSN: 1878-5077; 1878-5085; 1878-5085
• DOI: 10.1007/s13167-024-00357-5

Energy metabolism is a hub of governing all processes at cellular and organismal levels such as, on one hand, reparable vs. irreparable cell damage, cell fate (proliferation, survival, apoptosis, malignant transformation etc.), and, on the other hand, carcinogenesis, tumor development, progression and metastazing versus anti-cancer protection and cure. The orchestrator is the mitochondria who produce, store and invest energy, conduct intracellular and systemically relevant signals decisive for internal and environmental stress adaptation, and coordinate corresponding processes at cellular and organismal levels. Consequently, the quality of mitochondrial health and homeostasis is a reliable target for health risk assessment at the stage of reversible damage to the health followed by cost-effective personalized protection against health-to-disease transition as well as for targeted protection against the disease progression (secondary care of cancer patients against growing primary tumors and metastatic disease). The energy reprogramming of non-small cell lung cancer (NSCLC) attracts particular attention as clinically relevant and instrumental for the paradigm change from reactive medical services to predictive, preventive and personalized medicine (3PM). This article provides a detailed overview towards mechanisms and biological pathways involving metabolic reprogramming (MR) with respect to inhibiting the synthesis of biomolecules and blocking common NSCLC metabolic pathways as anti-NSCLC therapeutic strategies. For instance, mitophagy recycles macromolecules to yield mitochondrial substrates for energy homeostasis and nucleotide synthesis. Histone modification and DNA methylation can predict the onset of diseases, and plasma C7 analysis is an efficient medical service potentially resulting in an optimized healthcare economy in corresponding areas. The MEMP scoring provides the guidance for immunotherapy, prognostic assessment, and anti-cancer drug development. Metabolite sensing mechanisms of nutrients and their derivatives are potential MR-related therapy in NSCLC. Moreover, miR-495-3p reprogramming of sphingolipid rheostat by targeting Sphk1, 22/FOXM1 axis regulation, and A2 receptor antagonist are highly promising therapy strategies. TFEB as a biomarker in predicting immune checkpoint blockade and redox-related lncRNA prognostic signature (redox-LPS) are considered reliable predictive approaches. Finally, exemplified in this article metabolic phenotypi