Drug screening on tumor organoids exposes therapeutic vulnerabilities of meningiomas to HDAC1/2i panobinostat - PubMed
3 hours ago
- #organoid
- #panobinostat
- #meningioma
- Aggressive meningiomas have limited treatment options beyond surgery and radiotherapy.
- A drug screening workflow identified nine effective inhibitors from 107 targeted drugs tested.
- Patient-derived tumor organoids (TOs) were used to preserve the original tumor's genotype and phenotype for testing.
- Panobinostat, an FDA-approved epigenetic drug, showed high efficacy in 70% of TOs by inhibiting HDAC1/2.
- In vivo treatment with panobinostat improved survival in an orthotopic model.
- Resistance to panobinostat was linked to the HDAC8-TGFβ-EMT axis; HDAC8 depletion increased drug sensitivity.
- TOs are valuable for personalized drug screening and understanding resistance mechanisms in meningiomas.