LAUSR

Long-term drug evaluation heavily relies upon rodent models. Methods to reduce animal models in oncology may include three-dimensional cellular systems that take into account tumor microenvironment (TME) cell types and biomechanical properties. Innovative translational research is needed in low-grade serous ovarian cancer (LGSOC) in which the presence of oncogenic mutations in the RAS pathway likely suggest the opportunity to test targeted treatments. To address all these needs this study reports on an elastic polymer, to print a scaffold that mimics tissue relevant stiffness. Introduction of single cell suspensions from LGSOC patient-derived early passage cultures of cancer cells and cancer-associated fibroblast form heterocellular spheroids mimicking the growth ratio and spatial organization of the LGSOC TME. The resulting scaffold allows long-term (>40 days) follow-up and targeted compound evaluation confirmed the durable response to a drug combination. The drug-response results from this long-term in vitro model are compared with drug responses in an orthotopic LGSOC xenograft mouse model. In conclusion, the stiffness-tunable scaffolds colonized by a three-dimensional LGSOC TME allow long-term drug evaluation and can be considered as a valid alternative to reduce, replace and refine animal models in drug discovery. Citation Format: Elly De Vlieghere, Olivier De Wever. Long-term drug efficacy evaluation using stiffness-tunable scaffolds colonized by a three-dimensional tumor microenvironment. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4574.