Abstract
Gliomas represent a wide spectrum of brain tumors characterized by their high invasiveness, resistance to chemoradiotherapy, and both intratumoral and intertumoral heterogeneity. Recent advances in transomics studies revealed that enormous abnormalities exist in different biological layers of glioma cells, which include genetic/epigenetic alterations, RNA expressions, protein expression/modifications, and metabolic pathways, which provide opportunities for development of novel targeted therapeutic agents for gliomas. Metabolic reprogramming is one of the hallmarks of cancer cells, as well as one of the oldest fields in cancer biology research. Altered cancer cell metabolism not only provides energy and metabolites to support tumor growth, but also mediates the resistance of tumor cells to antitumor therapies. The interactions between cancer metabolism and DNA repair pathways, and the enhancement of radiotherapy sensitivity and assessment of radiation response by modulation of glioma metabolism are discussed herein.
Highlights
Over-expression of the facilitative GLUT1 protein has been observed in a large array of human cancer types suggesting that it likely plays a role in tumor initiation, progression and modulation of tumor immune microenvironment (TME) [38,39,40]
Recent advances in high-throughput technologies, have allowed us to classify gliomas into different categories based on their genetic and epigenetic lesions, instead of the histopathological classifications conventionally used by clinical pathologists
Intracellular glucose, lipid, amino acid, and nucleotide levels are dramatically upregulated through extracellular uptake, de novo synthesis, and other molecular mechanisms; in so doing, the metabolic reprogramming supports aggressive proliferation, progression, and chemoradiation resistance in gliomas
Summary
Irradiation can cause DNA damage in mammalian cells, which was first shown in a microelectrophoretic study almost four decades ago [4]. Reactive oxygen species (ROS) are generated in aerobic cells, but cells can utilize multiple mechanisms to balance the redox homeostasis and eliminate oxidative stress such as glutathione (GSH), superoxide dismutase (SOD). For radiation treatment of cancer, the cellular redox system may be a critical determinant to enhance cancer cell killing while protecting normal tissues because ROS can oxidize cellular biomolecules such as proteins and lipids and activate many pathological processes [8]. While this mechanism has largely remained uncharted, ROS generation can become one of the primary weapons of radiotherapy for radiation-induced death of cancer cells [9]. Due to the complexity of the cellular damages induced by radiation treatment, the biological systems have a limited ability to repair these damages, which provides the theoretical and experimental foundations of radiation treatment [10]
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