Abstract 1149P
Background
Patient-derived breast cancer organoids are valuable preclinical models to study patient drug responses, demonstrating a good correlation with patients’ clinical outcomes. However, the establishment and expansion of such organoids 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 breast cancer micro-organospheres (MOS). Drug sensitivities studies on MOS were performed using 10 FDA-approved drugs. The drug response of MOS and bulk organoids was assessed by CellTiter 3D Glo assay, while the growth and establishment of MOS were assessed using imaging analysis. The drug sensitivity of breast cancer MOS was analyzed by calculating percent viability and normalized growth rate inhibition (GRI) and compared to the response in bulk organoids and in vivo xenograft studies.
Results
We successfully established MOS from eight patient-derived breast cancer organoids with a 100% success rate. The MOS preserved similar cell morphologies to the bulk organoids. Out of 8 micro-organosphere models, 7 had similar drug response patterns to bulk organoids as evident by the GRI. Specifically, matching MOS and conventional bulk organoids from two patients with 10 frontline BC chemotherapy drugs showed a similar response to therapy. For the other 6 patient-derived models, the responses of MOS to Docetaxel and Everolimus also matched the historical drug responses in bulk organoid culture. Finally, drug sensitivity conducted in three MOS correlated to matching patient-derived xenografts (PDX).
Conclusions
In this study, we show a positive correlation in drug response between MOS, conventional bulk organoids, and PDX. Our microfluidic-based, patient-derived MOS assay, provides a rapid, scalable, and cost-effective platform to study drug sensitivity. This technology has the potential to be used for both diagnostics to guide patient treatment and as a screening platform for new breast cancer drug discovery.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Xiling Shen.
Funding
Xilis, Inc.
Disclosure
D. Nelson, C. Keating, A. Smith, D. Hsu, X. Shen: Financial Interests, Institutional, Stocks/Shares: Xilis, Inc. All other authors have declared no conflicts of interest.