Deciphering Drug Targets and Actions with Single-Cell and Spatial Resolution

Annu Rev Pharmacol Toxicol. 2023 Sep 18. doi: 10.1146/annurev-pharmtox-033123-123610. Online ahead of print.ABSTRACTRecent advances in chemical, molecular, and genetic approaches have provided us with an unprecedented capacity to identify drug-target interactions across the whole proteome and genome. Meanwhile, rapid developments of single-cell and spatial omics technologies are revolutionizing our understanding of the molecular architecture of biological systems. However, a significant gap remains in how we align our understanding of drug actions, traditionally based on molecular affinities, with the in vivo cellular and spatial tissue heterogeneity revealed by these newer techniques. Here, we review state-of-the-art methods for profiling drug-target interactions and emerging multiomics tools to delineate the tissue heterogeneity at single-cell resolution. Highlighting the recent technical advances enabling high-resolution, multiplexable in situ small-molecule drug imaging (clearing-assisted tissue click chemistry, or CATCH), we foresee the integration of single-cell and spatial omics platforms, data, and concepts into the future framework of defining and understanding in vivo drug-target interactions and mechanisms of actions. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 64 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.PMID:37722721 | DOI:10.1146/annurev-pharmtox-03...
Source: Annual Review of Pharmacology and Toxicology - Category: Drugs & Pharmacology Authors: Source Type: research