Targeting fuel pocket of cancer cell metabolism: A focus on glutaminolysis.

ABSTRACT

Advances in cell metabolism over the past few decades have demonstrated glutamine as an essential nutrient for cancer cell survival and proliferation. Glutamine offers a remarkable capacity to fuel diverse metabolic pathways in cancer cells including the Krebs cycle, maintenance of redox homeostasis, and synthesis of cellular building blocks such as nucleic acids, fatty acids, glutathione, and other amino acids. The increase in glutaminolysis has further been linked to the accumulation of oncometabolites such as 2HG (2-Hydroxyglutarate), succinate, fumarate, etc., thereby contributing to tumorigenesis via regulating epigenetic modification of imprinted genes. Therefore, therapeutic targeting of glutaminolysis in cancer cells is worth exploring for possible treatment strategies for cancer management. In this review, we have discussed the detailed mechanism of glutamine uptake, transport, and its instrumental role in rewiring the metabolic adaptation of cancer cells in the tumor microenvironment under nutrient deprivation and hypoxia. Furthermore, we have attempted to provide an updated therapeutic intervention of glutamine metabolism as a treatment strategy for cancer management.