Abstract B30: Ex vivo culture of breast cancer patient-derived xenografts in modified 3-D hyaluronan hydrogels

摘要: The high attrition rate of potential anti-cancer drugs entering clinical trials indicates the need for more predictive pre-clinical model systems. Standard compound screening is high-throughput and relatively inexpensive, but conducted with non-representative cells in a non-physiological environment. Three-dimensional (3D) culture systems provide physiological microenvironment including relevant extracellular matrix (ECM) cues cell-cell interactions. Patient-derived xenograft (PDX) preserves tumor heterogeneity while mitigating harsh selective pressures induced by traditional 2D methods. However, vivo mouse models are slow expensive, often low “take” rates that limit numbers drug combinations can be tested. Within present study, we established direct breast cancer PDX hyaluronan-based hydrogel amenable to automated dispensing. Washington University Human Mouse (WHIM) tumors were dissociated cell encapsulated 3D hydrogels vitro culture. In cultured showed viability over 7 days, as assessed standard live/dead assay. Cell morphology marker retention also examined using immunofluorescence staining markers ER, EpCAM, vimentin, found subtype-consistent. Ongoing studies seek expand matrices such they may useful variety applications screening, proteome kinome activation analysis, other will enable development personalized therapies suited individual patients presenting various disease subtypes. Citation Format: Lindsey K. Sablatura, MeghaShyam Kavuri, Priya Richards, Daniel A. Harrington, Matthew J. Ellis, Mary C. Farach-Carson. Ex patient-derived xenografts modified 3-D hyaluronan hydrogels. [abstract]. In: Proceedings AACR Special Conference on Advances Breast Cancer Research; Oct 17-20, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Res 2016;14(2_Suppl):Abstract nr B30.