Single-Cell Computational Frameworks for Quantifying BET Bromodomain Inhibitor Resistance and Screening Re-Sensitizer Drugs in Triple-Negative Breast Cancer - PubMed
4 hours ago
- #single-cell RNA sequencing
- #TNBC treatment
- #drug resistance
- Single-cell RNA sequencing (scRNA-seq) data was used to study BET bromodomain inhibitor (BBDI) resistance in triple-negative breast cancer (TNBC).
- Two computational frameworks, FR20 and D-FR20, were developed to quantify BBDI resistance at single-cell resolution and screen for re-sensitizer drugs.
- FR20's accuracy and scalability were validated across nine independent datasets, revealing ferroptosis inhibition in BBDI resistance evolution.
- Experimental validation showed that GPX4 overexpression reduces drug sensitivity in TNBC cells, linking ferroptosis to resistance.
- In vitro and in vivo experiments confirmed that filgotinib, identified by D-FR20, re-sensitizes BBDI and eliminates resistant TNBC cells.
- The study provides tools for predicting BBDI resistance and potential re-sensitizers, highlighting ferroptosis as a key factor in TNBC treatment.