Metabolic Pathways, Enzymes, and Metabolites: Opportunities in Cancer Therapy

SIMPLE SUMMARY: Deregulated cellular metabolism is one of the major hallmarks of cancer. Cancer cells orchestrate abnormal metabolic reprogramming to satisfy high energy demands. The review focuses on the mechanics of the major metabolic pathways, significant intermediates, and associated enzymes that are altered by the oncogenic progression. The emphasis is laid on therapeutically targeting clinically relevant metabolic intermediates which are crucial to cancer cell survival, and proliferation. The clinical intervention of metabolic pathways, critical enzymes, and the intermediate, thus offers a distinct niche in cancer therapies. ABSTRACT: Metabolic reprogramming enables cancer cells to proliferate and produce tumor biomass under a nutrient-deficient microenvironment and the stress of metabolic waste. A cancer cell adeptly undergoes a variety of adaptations in metabolic pathways and differential expression of metabolic enzyme genes. Metabolic adaptation is mainly determined by the physiological demands of the cancer cell of origin and the host tissue. Numerous metabolic regulators that assist cancer cell proliferation include uncontrolled anabolism/catabolism of glucose metabolism, fatty acids, amino acids metabolism, nucleotide metabolism, tumor suppressor genes, microRNAs, and many regulatory enzymes and genes. Using this paradigm, we review the current understanding of metabolic reprogramming in tumors and discuss the new strategies of cancer metabolomics that can be tapped into for cancer therapeutics.