Method Profile
Compare ASO uptake, HSP27 suppression and growth response in prostate cancer cells and patient-derived organoids under different delivery conditions.
Investigate whether drug access contributes to differences between two-dimensional and organoid pharmacology.
Patient-derived prostate cancer organoids and two-dimensional cancer-cell cultures.
Compare intact organoids with altered matrix and single-cell delivery conditions.
Patient-derived material
Prostate cancer organoids characterized histologically and molecularly against their source tumors.
Antisense drug
OGX-427 (apatorsen), an HSP27-targeting antisense oligonucleotide.
Follow delivery, target suppression and growth together when comparing 2D, intact 3D and altered-delivery conditions.
OGX-427 tested across 2D and 3D models with a matrix/delivery intervention.
A prostate cancer PDO collection and two-dimensional cultures.
Two-dimensional cultures, intact matrix-associated organoids and adjusted delivery conditions.
The limited intact-organoid response increased after matrix removal and single-cell delivery, with improved uptake, target suppression and dose-dependent growth inhibition.
An HSP27-targeting antisense drug suppressed its target in two-dimensional prostate cancer cultures but had limited activity in intact organoids. Changing matrix and delivery conditions improved uptake and restored dose-dependent growth inhibition.
