Abstract 1619: Personalized medicine: A CLIA-certified high-throughput drug screening platform for ovarian cancer
Authors: Swan Hallie A. , Rosati Rachele , Bridgwater Caroline , Churchill Michael J. , Watt Roland M. , Shaw Reid C. , Murphy Stephanie A. , Diaz Robert L. , Pereira Shalini C. , Schaub Franz X. , Grandori Carla 
Published: August 2018

Background:

Metastatic disease in ovarian cancer is difficult to treat and patients often exhaust standard-of-care regimens. To get a better understanding of potential treatments, genomic data is used in some cases. However, this only points to therapeutic options in a minority of cases highlighting an urgent need to develop assays to identify potential therapies. Current functional tests are limited in the number of tested drugs. Here we present the first CLIA certified high-throughput functional assay employing organoid cultures derived from primary patient specimens to directly aid oncologists for personalized treatment selection (P.A.R.I.S. Assay, SEngine Precision Medicine, Seattle, WA).

Experimental Procedures:

Organoids are treated for 6 days with a library of 123 clinically relevant drugs. Compounds are evaluated at a multi-dose response curve and ranked by SPM score, which weights both the sensitivity (degree of cell death) and specificity, which compares the patient's tumor cells response to the drug relative to all prior patients. The results are further integrated with genomic data and reported to the clinician to highlight treatment options. SEngine has performed &gt;150 drug screens and established high reproducibility including multiple ovarian cancer cases from either ascites, surgical or core biopsies.

Results:

Here we present two n-of-one patient studies. Patient 1 is a 48 year old woman with positive family history who was diagnosed with late stage serous ovarian cancer. SEngine generated cancer organoids and performed high-throughput screening with a panel of 123 drugs. Sensitivities to PARP inhibitors prompted SEngine to advise for germline testing which revealed a BRCA1 and TP53 mutation. The cells were also uniquely sensitive to paclitaxel and the combination with carboplatin resulted in remission indicating concordance with clinical data. In addition, highlighting the importance of functional screening, a unique response to a sub-group of EGFR inhibitors was identified, of potential consideration in case of recurrence.

The second case also has a family history of ovarian cancer, but no BRCA mutations were detected. Genomic data indicated FGF6 and FGF23 amplification which directly corresponded to a unique sensitivity to one FGFR inhibitor (AZD-4547). The organoids were also resistant to PARP inhibitors, consistent with the absence of BRCA mutations.

Impact:

We developed a robust ex vivo screening platform to objectively quantify patient specific sensitivity to a panel of 123 oncology drugs. SEngine is compiling a registry capturing clinical data, outcome following the P.A.R.I.S. test as well as genomic data. The power of high throughput technology and organoid isolation will enable the rapid selection of optimal individualized therapies as single agents or in combination.

Citation Format: Hallie A. Swan, Rachele Rosati, Caroline Bridgwater, Michael J. Churchill, Roland M. Watt, Reid C. Shaw, Stephanie A. Murphy, Robert L. Diaz, Shalini C. Pereira, Franz X. Schaub, Carla Grandori. Personalized medicine: A CLIA-certified high-throughput drug screening platform for ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1619.