ScDrugAct: a comprehensive database to dissect tumor microenvironment cell heterogeneity contributing to drug action and resistance across human cancers

The transcriptional heterogeneity of tumor microenvironment (TME) cells is a crucial factor driving the diversity of cellular response to drug treatment and resistance. Therefore, characterizing the cells associated with drug treatment and resistance will help us understand therapeutic mechanisms, discover new therapeutic targets and facilitate precision medicine. Here, we describe a database, scDrugAct (http://bio-bigdata.hrbmu.edu.cn/scDrugAct/), which aims to establish connections among drugs, genes and cells and dissect the impact of TME cellular heterogeneity on drug action and resistance at single-cell resolution. ScDrugAct is curated with drug-cell connections between 3838 223 cells across 34 cancer types and 13 857 drugs and identifies 17 274 drug perturbation/resistance-related genes and 276 559 associations between >10 000 drugs and 53 cell types. ScDrugAct also provides multiple flexible tools to retrieve and analyze connections among drugs, genes and cells; the distribution and developmental trajectories of drug-associated cells within the TME; functional features affecting the heterogeneity of cellular responses to drug perturbation and drug resistance; the cell-specific drug-related gene network; and drug-drug similarities. ScDrugAct serves as an important resource for investigating the impact of the cellular heterogeneity of the TME on drug therapies and can help researchers understand the mechanisms of action and resistance of drugs, as well as discover therapeutic targets.