Energy metabolism in bone tumors: Fuel selection and adaptation

Abstract

It has long been recognized that cancer cells exhibit altered patterns of metabolism that allow them to meet the biosynthetic demands of rapid proliferation and overcome metabolic stress imposed by the microenvironment. In this chapter, we aim to recapitulate knowledge on energetic metabolism and reprogramming in osteo-oncology. Diagnosis and staging of bone metastases using 18 Fluorine labeled glucose, choline, and folate and emission tomography and computerized tomography (PET/CT) reflect tumor cells energetic metabolism. Metabolites and associated gene regulators involved in bone metastases and/or osteosarcoma progression are also described, including glucose, lactate, amino acid, cholesterol, fatty acids, and derived mitochondrial activity reactive oxygen species. Moreover several master regulators of energy metabolism in normal physiology, metabolic syndromes, and cancer (PPARγ, ERRα, PGC1α, CREB, MYC, RAS, EWS-FLI, TMPRSS2-ERG, and mTOR) are identified in bone metastases and primary bone tumor. Interestingly, factors that were first detected in bone physiology (RANKL/OPG/RANK, Runx2, OPN, OCN, POSTN, and SOST) have been recently identified as regulators of energetic metabolism. Finally, in clinic, treatments targeting metabolism (everolimus, statin, etc.) have an impact on bone metastases regression, suggesting that targeting energetic metabolism may constitute a new therapeutic pathway in osteo-oncology.