Abstract 183: Ex vivo 3D drug response profiling of XPDX-derived tumor cells for acceleration of preclinical drug development

Abstract

Abstract Patient-Derived Xenografts (PDX) represent a versatile tool for preclinical drug development because they recapitulate many key features of the parent tumors, including molecular and histopathological profiles, tumor microenvironment, and tumor heterogeneity. The clinical relevance of PDX thus offer several advantages over other commonly used tools such as cell lines and genetically modified mice. Many large collections of PDX have been developed across a wide range of tumor types that profile the genetic diversity of each disease and the ability to bank PDX material allows repeated generation of mice for in vivo drug screens. As a result, PDX are used in several parts of the drug development pipeline, including early cancer biology studies, biomarker development, evaluation of therapeutic efficacy, and assessing/overcoming drug resistance. However, there remain drawbacks to this approach, most notably the large number of mice required for comprehensive drug screens and the associated time and costs. One approach to streamline PDX model selection and in vivo study execution would be to predict in vivo drug responses by assessing responses to the same drugs in an ex vivo platform utilizing PDX-derived dissociated tumor cells. KIYATEC’s KIYA-PREDICT™ PDX assay is a 3D spheroid-based ex vivo platform that has been used to screen a wide range of drugs and tumor types to predict drug responses in primary patient-derived tumors and PDX-derived tumors, including several PDX from XenoSTART’s extensive library of XPDX models. Here, we dissociated XPDX-derived tumors from a panel of 20 breast, ovarian, and lung cancer models provided by XenoSTART and evaluated their ex vivo responses to a panel of chemotherapy agents in our 3D KIYA-PREDICT™ assay. After exposure to drugs for 3-7 days, viability was assessed and both IC50s and percent survival values were calculated. The percent survival was then compared to in vivo drug response data provided by XenoSTART, and correlations between in vivo and ex vivo data were assessed. Drug responses were highly correlative between ex vivo and in vivo models, including the ability to recapitulate palbociclib resistance and platinum and taxane response. These results indicate that the KIYA-PREDICT™ PDX assay is a valuable tool to incorporate into drug development pipelines to accelerate the screening of new drug compounds on a wide range of clinically relevant samples and to guide selection of PDX models for in vivo studies. Citation Format: Aaron L. Carlson, Ashley K. Elrod, Natalie A. Williams, Alyssa D. Moriarty, Michael J. Wick, Teresa M. DesRochers. Ex vivo 3D drug response profiling of XPDX-derived tumor cells for acceleration of preclinical drug development [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 183.