Abstract 6209: TumOC: A tumor organoid-on-chip platform for real-time cell vitality measurements

Abstract

Abstract Colorectal carcinomas (CRC) are one of the most common malignant tumors. Due to its heterogeneity and high probability to metastasize, the disease is often incurable and novel, improved therapies are needed. Enhanced, physiologically relevant in-vitro tumor models significantly increase the success rate in new drug development, reduce the number of animal experiments and result finally in better therapies for cancer patients. Furthermore, they have the potential to offer new approaches to personalized oncology. In recent years, 3D cell cultures were established as relevant preclinical cancer models, suitable for high-throughput-screening. However, their capacity to model and/or measure physiological processes can still be enhanced. In this project, we developed a tumor organoid-on-chip platform (TumOC) by combining most recent technological advances: We integrated patient-derived 3D cell cultures (organoids) from colorectal carcinomas and microsensor particles measuring oxygen concentration and therefore allowing assessment of cell vitality in real time in a microfluidic system. The resulting TumOC platform allows for defined exposition of cytostatic drugs including dynamic treatments. Measurements of cell vitality in real time enables analysis of not only the final effect of a drug treatment, but also the kinetics of drug response. At the same time, utilizing organoids allows for recapitulating tumor architecture and heterogeneity. Here we report the first proof of principle results generated with this system. We measured the cell vitality in real time over 72 hours during treatment with classic chemotherapeutics or targeted cancer drugs and compared the results to end-point measurements on the same organoids in a static system. In conclusion, our TumOC platform with its ability to recapitulate tumor heterogeneity in combination with dynamic treatments and real-time cell vitality assessment is an in-vitro tumor model closely recapitulating the physiological situation in a patient. TumOC provides an impressive opportunity to test and, consequently, predict the effectiveness of anti-cancer therapies. Therefore, this system is of interest not only for pre-clinical drug development but also for personal oncology. Citation Format: Marie Flechner, Juergen Loskutov, Ulrike Pfohl, Katja Osman, Christian R. Regenbrecht, Katja Uhlig, Lena Wedeken. TumOC: A tumor organoid-on-chip platform for real-time cell vitality measurements [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6209.