Most patients with advanced
ovarian cancer (OC) relapse and progress despite systemic
therapy, pointing to the need for improved and tailored
therapy options. Functional
precision medicine can help to identify effective
therapies for individual patients in a clinically relevant timeframe. Here, we present a scalable functional
precision medicine platform: DET3Ct (
Drug Efficacy Testing in 3D Cultures), where the response of patient cells to drugs and
drug combinations are quantified with live-cell imaging. We demonstrate the delivery of individual
drug sensitivity profiles in 20 samples from 16 patients with
ovarian cancer in both 2D and 3D culture formats, achieving over 90% success rate in providing results six days after operation. In this cohort all patients received
carboplatin. The
carboplatin sensitivity scores were significantly different for patients with a progression free interval (PFI) less than or equal to 12 months and those with more than 12 months (p < 0.05). We find that the 3D culture format better retains proliferation and characteristics of the in vivo setting. Using the DET3Ct platform we evaluate 27 tailored combinations with results available 10 days after operation. Notably,
carboplatin and
A-1331852 (Bcl-xL inhibitor) showed an additive effect in four of eight OC samples tested, while
afatinib and
A-1331852 led to synergy in five of seven OC models. In conclusion, our 3D DET3Ct platform can rapidly define potential, clinically relevant data on efficacy of existing drugs in OC for
precision medicine purposes, as well as provide insights on emerging drugs and
drug combinations that warrant testing in clinical trials.