Allosteric regulation of metabolism in cancer: endogenous mechanisms and considerations for drug design

•Altered allosteric mechanisms underlie metabolic phenotypes in disease.•Metabolite concentrations and oncogenic signalling converge to influence allostery.•Protein dynamics carry allosteric information.•Understanding protein dynamics will aid targeting allostery for therapy.

Alterations in metabolic processes have been linked to various diseases, including cancer. Although gene expression can dictate long-term metabolic adaptation, many metabolic changes found in cancer are associated with altered allosteric properties of the underlying enzymes. Small molecule-protein interactions and intracellular signalling converge to orchestrate these allosteric mechanisms, which, emerging evidence suggests, constitute a promising therapeutic avenue. In this review we focus on glucose and energy metabolism to illustrate the role of allostery in cancer physiology and we discuss approaches to streamline the process of targeting aberrant allosteric pathways with small molecules.

Graphical abstractDownload high-res image (101KB)Download full-size image