Metabolic reprogramming is one of the hallmarks of tumors. Alterations of cellular metabolism not only contribute to tumor development, but also mediate the resistance of tumor cells to antitumor drugs. The metabolic response of tumor cells to various chemotherapy drugs can be analyzed by metabolomics. Although cancer cells have experienced metabolic reprogramming, the metabolism of drug resistant cancer cells has been further modified. Metabolic adaptations of drug resistant cells to chemotherapeutics involve redox, lipid metabolism, bioenergetics, glycolysis, polyamine synthesis and so on. The proposed metabolic mechanisms of drug resistance include the increase of glucose and glutamine demand, active pathways of glutaminolysis and glycolysis, promotion of NADPH from the pentose phosphate pathway, adaptive mitochondrial reprogramming, activation of fatty acid oxidation, and up-regulation of ornithine decarboxylase for polyamine production. Several genes are associated with metabolic reprogramming and drug resistance. Intervening regulatory points described above or targeting key genes in several important metabolic pathways may restore cell sensitivity to chemotherapy. This paper reviews the metabolic changes of tumor cells during the development of chemoresistance and discusses the potential of reversing chemoresistance by metabolic regulation.

Pyruvate kinase is a terminal enzyme in the glycolytic pathway, where it catalyzes the conversion of phosphoenolpyruvate to pyruvate and production of ATP via substrate level phosphorylation. PKM2 is one of four isoforms of pyruvate kinase and is widely expressed in many types of tumors and associated with tumorigenesis. In addition to pyruvate kinase activity involving the metabolic pathway, increasing evidence demonstrates that PKM2 exerts a non-metabolic function in cancers. PKM2 has been shown to be translocated into nucleus, where it serves as a protein kinase to phosphorylate various protein targets and contribute to multiple physiopathological processes. We discuss the nuclear localization of PKM2, its protein kinase function and association with cancers, and regulation of PKM2 activity.

Radiation caries is a complication of radiotherapy characterized by enamel erosion and dentin exposure. The mechanisms of characteristic radiation caries formation are not well-understood. The aim of this study was to evaluate the direct radiation-induced effects on dental hard tissue and investigate their role in the formation of radiation caries. Sixty non-carious third molars were divided into three groups (n = 20), which would be exposed to 0 Gy, 30 Gy, and 60 Gy radiation, respectively. After radiation, microhardness and elastic modulus were measured at four depths by means of a Vickers microhardness tester and atomic force microscopy (AFM). The microstructure was observed by scanning electron microscopy (SEM). X-ray diffraction and Raman microspectroscopy were used to determine crystal properties and protein/mineral (2931/960 cm− 1) ratios. A statistically significant decrease in microhardness and elastic modulus values 50 μm from the dentino-enamel junction (DEJ) in enamel was revealed in the 30-Gy and 60-Gy groups. With the increasing dose, destruction of interprismatic substance and fissures at the DEJ-adjacent region were found. A greater reduction of crystallinity was revealed in enamel compared with dentin. Raman spectroscopic analysis showed a slight increase of the protein/mineral ratio for enamel following accumulated radiation, while the protein/mineral ratio for dentin was decreased. Radiation could directly alter the mechanical properties, micro-morphology, crystal properties, and chemical composition of dental hard tissue. The early destruction of DEJ-adjacent enamel, combined with decreased crystallinity of enamel under radiation exposure, may be related to the formation of characteristic radiation caries.