Micro-organospheres: An automated patient-derived model platform for rapid drug screening of breast cancer.

Abstract

e12628 Background: Patient-derived breast cancer (BC) organoids are valuable preclinical models to study patient drug responses, demonstrating good correlations with patients’ clinical outcomes. However, establishment and expansion of such organoids from patient tumors for drug screening is currently a time-consuming and labor-intensive process. A more rapid and high-throughput method will enable broader utility in diagnostics and drug development. Methods: An automated, rapid and scalable microfluidic platform was used to process and develop BC micro-organospheres. Drug sensitivities studies on BC micro-organospheres were performed on day 3 and day 6 using 10-FDA approved drugs, including palbociclib, adriamycin, 5-FU, gemcitabine, methotrexate, everolimus, paclitaxel, docetaxel, ixabepilone, and vinblastine. The responses of micro-organospheres and organoids to the drugs were assessed by CellTiter 3D Glo assay on day 6 after the drug treatment. The growth and establishment of the micro-organospheres by imaging. The drug sensitivity and resistance of the micro-organospheres were analyzed by calculating the percentage cell viability and normalized growth rate inhibition (GRI) and compared to organoids. Results: We successfully established micro-organospheres from eight patient-derived BC organoids with a 100% success rate. The micro-organospheres preserved similar cell morphologies to the bulk organoids. 7/8 micro-organosphere models had similar drug response patterns to organoids between day 3 and day 6 as evident by the GRI heatmap. Specifically, we treated matching micro-organospheres and conventional organoids from two patients with 10 frontline BC chemotherapy drugs, and both showed similar response patterns with GRI heatmap. For the other 6 patient-derived models, the responses of micro-organospheres to docetaxel and everolimus also matched the historical drug responses of in bulk organoid culture with similar GRI heatmap. Conclusions: We have now shown the feasibility of establishing micro-organospheres as a rapid, scalable, and cost-effective platform to study patient-derived BC drug response. This technology has the potential to be used for both diagnostics to guide patient treatment and as a screening platform for new BC drug discovery.