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Updated: Jul 10, 2025
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
DRMref: comprehensive reference map of drug resistance mechanisms in human cancer
Xiaona Liu1, Jiahao Yi2, Tina Li1
1Center for Computational Systems Medicine, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Abstract:
Drug resistance poses a significant challenge in cancer treatment. Despite the initial effectiveness of therapies such as chemotherapy, targeted therapy and immunotherapy, many patients eventually develop resistance. To gain deep insights into the underlying mechanisms, single-cell profiling has been performed to interrogate drug resistance at cell level. Herein, we have built the DRMref database (https://ccsm.uth.edu/DRMref/) to provide comprehensive characterization of drug resistance using single-cell data from drug treatment settings. The current version of DRMref includes 42 single-cell datasets from 30 studies, covering 382 samples, 13 major cancer types, 26 cancer subtypes, 35 treatment regimens and 42 drugs. All datasets in DRMref are browsable and searchable, with detailed annotations provided. Meanwhile, DRMref includes analyses of cellular composition, intratumoral heterogeneity, epithelial-mesenchymal transition, cell-cell interaction and differentially expressed genes in resistant cells. Notably, DRMref investigates the drug resistance mechanisms (e.g. Aberration of Drug's Therapeutic Target, Drug Inactivation by Structure Modification, etc.) in resistant cells. Additional enrichment analysis of hallmark/KEGG (Kyoto Encyclopedia of Genes and Genomes)/GO (Gene Ontology) pathways, as well as the identification of microRNA, motif and transcription factors involved in resistant cells, is provided in DRMref for user's exploration. Overall, DRMref serves as a unique single-cell-based resource for studying drug resistance, drug combination therapy and discovering novel drug targets.
Insights
The DRMref database offers a comprehensive single-cell resource to understand cancer drug resistance mechanisms. It analyzes cellular changes and molecular pathways involved in treatment failure, aiding in developing new therapies.
Area of Science:
- Oncology
- Genomics
- Bioinformatics
Background:
- Drug resistance is a major obstacle in cancer therapy, limiting the efficacy of chemotherapy, targeted therapy, and immunotherapy.
- Single-cell profiling provides a powerful approach to dissect drug resistance mechanisms at an individual cell level.
Purpose of the Study:
- To establish DRMref, a centralized database for single-cell data characterizing drug resistance in cancer.
- To provide a searchable and browsable resource for researchers investigating the complexities of cancer drug resistance.
Main Methods:
- Compilation of 42 single-cell datasets from 30 studies, encompassing 13 cancer types and 42 drugs.
- Analysis of cellular composition, intratumoral heterogeneity, epithelial-mesenchymal transition, and cell-cell interactions in resistant cells.
- Investigation of drug resistance mechanisms, pathway enrichment (hallmark, KEGG, GO), and identification of regulatory elements (microRNA, transcription factors).
Main Results:
- DRMref integrates diverse single-cell data, offering detailed annotations and analyses relevant to drug resistance.
- The database facilitates the exploration of specific resistance mechanisms, such as target aberration and drug inactivation.
- Comprehensive analyses reveal key molecular players and pathways implicated in cellular resistance to cancer treatments.
Conclusions:
- DRMref serves as a unique, single-cell-based resource for advancing the study of cancer drug resistance.
- The database supports research into novel drug targets and the development of effective drug combination therapies.
- DRMref empowers researchers to explore intricate resistance mechanisms and identify potential therapeutic strategies.
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