Patient-derived scaffolds as a drug-testing platform for endocrine therapies in breast cancer
Three-dimensional (3D) cell culture systems based on decellularized, patient-derived microenvironments closely mimic in vivo conditions, enabling cancer cells to interact with native tissue structures and components. In this study, a patient-derived scaffold (PDS) model was evaluated as a platform for testing endocrine therapies—(Z)-4-Hydroxytamoxifen (4OHT) and fulvestrant—as well as the CDK4/6 inhibitor palbociclib, using the breast cancer cell lines MCF7 and T47D adapted to patient-specific microenvironments.
MCF7 cells cultured in PDSs displayed significantly increased resistance to 4OHT and fulvestrant—approximately 100-fold and 20-fold, respectively—compared to traditional 2D cultures. Quantitative PCR analyses revealed upregulation of pluripotency markers in endocrine-treated cells within the PDS, which correlated with enhanced self-renewal capacity observed in sphere formation assays.
When comparing various 3D culture platforms—including PDSs, Matrigel, gelatin sponges, and 3D-printed hydrogels—treatment responses to fulvestrant and palbociclib varied slightly. Notably, PDS and Matrigel cultures exhibited more similar gene expression profiles in response to 4OHT compared to other platforms.
These findings highlight the potential of the PDS model as a scalable, patient-specific drug testing platform. The ability to generate multiple functional PDS replicates from a single primary breast tumor makes it suitable for high-throughput gene expression analysis and downstream functional assays.