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Author Spotlight: Cost-Effective Transcriptomic Drug Screening - Unlocking New Targets
Published on: February 23, 2024
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A multiplex single-cell RNA-Seq pharmacotranscriptomics pipeline for drug discovery.
Alice Dini1, Harlan Barker1,2, Emilia Piki1
1Disease Networks Unit, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
Nature Chemical Biology
|November 1, 2024
Summary
We developed a new method for high-throughput drug screening in cancer cells using single-cell RNA sequencing. This approach revealed a feedback loop in ovarian cancer drug resistance that can be overcome with combination therapy.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- Understanding gene-regulatory dynamics in cancer drug responses is crucial.
- Current methods lack high-throughput single-cell resolution for pharmacotranscriptomics.
Purpose of the Study:
- To develop and validate a high-throughput pharmacotranscriptomic profiling pipeline.
- To explore drug responses and resistance mechanisms in high-grade serous ovarian cancer (HGSOC) at single-cell resolution.
Main Methods:
- Live-cell barcoding with antibody-oligonucleotide conjugates.
- 96-plex single-cell RNA sequencing combined with drug screening.
- Analysis of transcriptional landscape in HGSOC cells treated with 45 drugs.
Main Results:
- Identified a drug resistance feedback loop involving PI3K-AKT-mTOR inhibitors, EGFR activation, and CAV1 upregulation.
- Demonstrated that synergistic inhibition of PI3K-AKT-mTOR and EGFR can overcome resistance in HGSOC with specific biomarkers.
- Showcased the heterogeneity of cellular responses to various drug classes.
Conclusions:
- The developed pipeline enables high-throughput, single-cell pharmacotranscriptomic profiling.
- Revealed a targetable feedback loop in HGSOC drug resistance.
- This workflow facilitates personalized medicine approaches for cancer treatment testing.
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