Functional profiling of ovarian cancer models reveals Bcl-xL/NOTCH targeting to overcome resistance.
Researchers identified which ovarian cancer cells depend on a specific survival protein and found drugs that re-sensitize resistant tumors to standard chemotherapy.
Functional drug profiling of 35 patient-derived ovarian cancer models across 528 compounds identifies Bcl-xL dependency in a subset with favorable therapeutic window, while proteomics reveals NOTCH signaling as the resistance determinant. Gamma-secretase inhibitors restore Bcl-xL sensitivity and re-sensitize platinum-resistant models to carboplatin, establishing a clinically actionable co-targeting strategy.
What the study was
- Study design
- original_research
- Population
- 35 patient-derived ovarian cancer models from 22 patients, 7 OC subtypes
- Sample size
- 35
- Category
- Precision Oncology
- Maturity
- Exploratory
- Journal
- NPJ Precis Oncol
Why it surfaced
35 patient-derived OC models, 29,000+ drug response measurements across 528 compounds; NOTCH-modulated Bcl-xL vulnerability as actionable target in platinum-resistant OC; gamma-secretase + Bcl-xL restores platinum sensitivity; NPJ Precis Oncol; Karolinska SciLifeLab.
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