A functional precision medicine 3D microtumor platform to identify and personalize novel indications.

Abstract

e15588 Background: We have previously validated our 3D microtumor platform that captures the tumor heterogeneity of a patient's primary tumor biopsy using a patient-derived xenograft model (Nikolov et al. ASCO 2019, e17076). Here we describe its utility to identify FDA approved therapies that may be effective for tumors previously not considered. Methods: A fresh tumor sample of a liver metastasis of a 45-year-old colorectal cancer patient was shipped overnight and processed to create hundreds of live 3D microtumors. These microtumors were treated with a panel of 12 commonly used drugs including chemotherapies and targeted therapies. Treatment effects were quantified and validated on fresh and cryopreserved/thawed samples using our metabolic and proprietary multiplexed fluorescent staining technologies to quantify the ratio of live and dead cells in those microtumors. Results: None of the conventional treatments in the 12-panel drug test suggested any efficacy as determined by the log of efficacy concentrations (in µmol/l): Oxaliplatin 2.59, 5-FU 3.00 (upper cut-off value), paclitaxel 1.72, topotecan 3.00, irinotecan (SN-38) 2.33, gemcitabine 2.44, and bevacizumab 3.00. The microtumors also appeared resistant to several targeted therapies that are not commonly given, ranging from 1.85 to 2.44. However, abemaciclib had an efficacy of 0.49, which was confirmed on thawed samples with all drug efficacy concentrations again suggesting resistance, except for abemaciclib at 0.67. Conclusions: Our 3D microtumor platform may be a useful tool a) to identify rescue treatment options for metastatic patients that have multi-resistant tumors and b) to identify novel indications to personalize FDA-approved cytotoxic or targeted therapies as a companion diagnostic.