Abstract 358: In vitro assessment of tumor relapse in a 3D tumor microtissue model

Abstract

Abstract One of the most pressing problems in the treatment of cancer is tumor relapse. Although many tumors regress in response to neoadjuvant chemotherapy, residual tumor cells are detected in most cancer patients post-treatment. These residual tumor cells are thought to remain dormant for years before resuming growth, resulting in tumor recurrence. Considering that recurrent tumors are most often responsible for patient mortality, there exists an urgent need to study signaling pathways that drive tumor dormancy/recurrence. Current in vitro assays based on monolayer cultures do not provide the required time frame to study tumor recurrence. We developed a new method to study tumor relapse in a 3D in vitro tumor microtissue model. HCT116 colorectal tumor microtissues were produced and dosed with 3 reference compounds, Taxol (cell division inhibitor), Staurosporine (protein kinase inhibitor) and Doxorubicin (DNA synthesis inhibitor). Based on an initial range finding to determine IC20 and IC50 values, tumor growth was monitored via size profiling and viability (intra-tissue ATP content) over 10 days. Three different conditions were tested: (i) continuous treated tumor microtissues, (ii) microtissues which were supplemented with the drug for 5 days and (iii) non-treated tumor microtissues. Growth differences couldn't be observed comparing IC20 concentrations, however growth profiles significantly varied comparing IC50 concentrations. Whereas a 5-day treatment of Taxol was leading to a complete growth inhibition after removing the drug, Staurosporine treated tumor microtissues relapsed even with a similar growth kinetic as the untreated control group. Pulsed treatment of Doxorubicin was leading to a slower growth kinetic as compared to the control but not to a complete reminiscence. Based on the individual growth profiles relative to the continuous treated and non-treated groups we calculated a relapse index (ReI, patent pending) to enable classification of compounds and compound combinations according to their risk for tumor relapse. Here we present a novel in vitro tumor relapse assay method based on a 3-dimensional tumor microtissue model, to enable compound classification based on their efficiency to prevent tumor relapse. Citation Format: Sumeer Dhar. In vitro assessment of tumor relapse in a 3D tumor microtissue model. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 358.