Targeting galectin-driven regulatory circuits in cancer and fibrosis

KARINA MARIÑO ; ALEJANDRO CAGNONI ; DIEGO CROCI; GABRIEL RABINOVICH

NATURE REVIEWS DRUG DISCOVERY

NATURE PUBLISHING GROUP

Lugar: Londres; Año: 2023

1474-1776

Galectins are a family of endogenous glycan-binding proteins thathave crucial roles in a broad range of physiological and pathologicalprocesses. As a group, these proteins use both extracellular andintracellular mechanisms as well as glycan-dependent and independentpathways to reprogramme the fate and function of numerous cell types.Given their multifunctional roles in both tissue fibrosis and cancer,galectins have been identified as potential therapeutic targets for thesedisorders. Here, we focus on the therapeutic relevance of galectins,particularly galectin 1 (GAL1), GAL3 and GAL9 to tumour progressionand fibrotic diseases. We consider an array of galectin-targetedstrategies, including small-molecule carbohydrate inhibitors, naturalpolysaccharides and their derivatives, peptides, peptidomimetics andbiological agents (notably, neutralizing monoclonal antibodies andtruncated galectins) and discuss their mechanisms of action, selectivityand therapeutic potential in preclinical models of fibrosis and cancer. Wealso review the results of clinical trials that aim to evaluate the efficacyof galectin inhibitors in patients with idiopathic pulmonary fibrosis,nonalcoholic steatohepatitis and cancer. The rapid pace of glycobiologyresearch, combined with the acute need for drugs to alleviate fibroticinflammation and overcome resistance to anticancer therapies, willaccelerate the translation of anti-galectin therapeutics into clinicalpractice.