The hexosamine biosynthetic pathway and cancer: Current knowledge and future therapeutic strategies

The hexosamine biosynthetic pathway (HBP) is a glucose metabolism pathway that results in the synthesis of a nucleotide sugar UDP-GlcNAc, which is subsequently used for the post-translational modification (O-GlcNAcylation) of intracellular proteins that regulate nutrient sensing and stress response. The HBP is carried out by a series of enzymes, many of which have been extensively implicated in cancer pathophysiology. Increasing evidence suggests that elevated activation of the HBP may act as a cancer biomarker. Inhibition of HBP enzymes could suppress tumor cell growth, modulate the immune response, reduce resistance, and sensitize tumor cells to conventional cancer therapy. Therefore, targeting the HBP may serve as a novel strategy for treating cancer patients. Here, we review the current findings on the significance of HBP enzymes in various cancers and discuss future approaches for exploiting HBP inhibition for cancer treatment.

Automated summary

The hexosamine biosynthetic pathway (HBP) is a glucose metabolism pathway that results in the synthesis of UDP-GlcNAc, which can be used for post-translational modification of intracellular proteins. Activation of HBP has been implicated in cancer pathophysiology, and inhibition of HBP enzymes may serve as a novel strategy for cancer treatment by suppressing tumor growth and modulating immune response. Targeting HBP could potentially enhance sensitivity of tumor cells to conventional cancer therapy.