Galectins are a family of endogenous glycan-binding proteins that have crucial roles in a broad range of physiological and pathological processes. As a group, these proteins use both extracellular and intracellular mechanisms as well as glycan-dependent and independent pathways 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 these disorders. Here, we focus on the therapeutic relevance of galectins, particularly galectin 1 (GAL1), GAL3 and GAL9 to tumour progression and fibrotic diseases. We consider an array of galectin-targeted strategies, including small-molecule carbohydrate inhibitors, natural polysaccharides and their derivatives, peptides, peptidomimetics and biological agents (notably, neutralizing monoclonal antibodies and truncated galectins) and discuss their mechanisms of action, selectivity and therapeutic potential in preclinical models of fibrosis and cancer. We also review the results of clinical trials that aim to evaluate the efficacy of galectin inhibitors in patients with idiopathic pulmonary fibrosis, nonalcoholic steatohepatitis and cancer. The rapid pace of glycobiology research, combined with the acute need for drugs to alleviate fibrotic inflammation and overcome resistance to anticancer therapies, will accelerate the translation of anti-galectin therapeutics into clinical practice.

For decades, preclinical toxicology was essentially a descriptive discipline in which treatment-related effects were carefully reported and used as a basis to calculate safety margins for drug candidates. In recent years, however, technological advances have increasingly enabled researchers to gain insights into toxicity mechanisms, supporting greater understanding of species relevance and translatability to humans, prediction of safety events, mitigation of side effects and development of safety biomarkers. Consequently, investigative (or mechanistic) toxicology has been gaining momentum and is now a key capability in the pharmaceutical industry. Here, we provide an overview of the current status of the field using case studies and discuss the potential impact of ongoing technological developments, based on a survey of investigative toxicologists from 14 European-based medium-sized to large pharmaceutical companies.