Abstract 1782P
Background
Patient-derived organoids (PDO) have been shown to have a high degree of similarity to the original patient tumors. PDO have also been used to perform high throughput drug screens and shown to correlate with patient response to therapy. Unfortunately, PDO require too much tissue and are too inefficient and costly for adoption into the clinic. The ideal assay would be one that could be performed <14 days from a core biopsy to minimize delay in therapy. We have now circumvented these barriers by leveraging recent technological advances in emulsion microfluidics and droplet generators to develop Micro-OrganoSpheres (MOS) that can be established and used to predict drug sensitivity within 14 days of biopsy.
Methods
18 gauge core biopsy specimen from patients with metastatic colorectal cancer who subsequently received an oxaliplatin based therapy were first obtained. Biopsy specimen was minced, enzymatically digested and mixed with matrigel. The mixture was then processed through a custom fabricated flow-focusing droplet microfluidic chip to generate MOS. After culturing for 8-10 days, MOS were used to perform drug screen with oxaliplatin.
Results
A total of 12 CRC samples were processed with a success rate of 12/12 (100%) in generating MOS. Furthermore, drug screen was performed on all 12 samples with an average time to drug screen of 10.1 days. For the first eight patients, MOS was used to predict sensitivity to oxaliplatin. 4 patients were predicted to be sensitive to oxaliplatin and 4 patients were predicted to be resistant. Patients predicted to be sensitive to oxaliplatin continue to be on treatment (> 6 months), whereas 3 of the four patients predicted to be resistant to oxaliplatin progressed on oxaliplatin based therapy within 8 weeks (sensitivity = 80%, specificity = 100%, positive predictive value = 100%, negative predictive value = 75%).
Conclusions
MOS can be generated from core biopsies and correlates to time on treatment. The ability to generate MOS and perform a drug screen in <14 days will allow for the development of a precision oncology platform that can be rapidly used in the clinic to guide therapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Duke University.
Disclosure
D. Delubac: Financial Interests, Personal and Institutional, Ownership Interest: Xilis, Inc; Financial Interests, Personal, Stocks/Shares: Guardant Health; Financial Interests, Personal, Stocks/Shares: Freenome; Financial Interests, Personal, Stocks/Shares: IDByDNA; Financial Interests, Personal, Stocks/Shares: SpringDiscovery; Financial Interests, Personal, Stocks/Shares: Delfi; Financial Interests, Personal, Advisory Role: IDByDNA; Financial Interests, Personal, Advisory Role: Spring Discovery; Financial Interests, Personal, Advisory Role: Delfi; Financial Interests, Personal, Advisory Role: CareDx. X. Shen: Financial Interests, Personal and Institutional, Ownership Interest: Xilis, Inc. D. Hsu: Financial Interests, Personal and Institutional, Ownership Interest: Xilis, Inc. All other authors have declared no conflicts of interest.