Traditional HTS that utilize lab-adapted cell lines in high density cell plates do not sufficiently recapitulate the complex biological environment and thus do not translate well to <i>in vivo</i> and clinical outcomes. Complex models on well-plates such as iPSC-derived cell types, patient organoids, and multicellular systems are increasingly adopted as they are more predictive, disease relevant, and will eventually reduce the drug attrition rates when employed early in the drug discovery & development process. As an exemplar of scale-able human-relevant complex model for screening, we systematically developed a triculture system of non-small cell lung cancer (NSCLC) incorporating cancer associated cells such as lung fibroblasts and bronchiolar epithelial cells, and, components of the extracellular matrix (ECM), in the context of drug combination screen with Poly(ADP-ribose) polymerase (PARP) inhibitors. Tumor cell cytotoxicity was assessed via inherent fluorescent expression by high content analysis (HCA) across drug resistant and sensitive cell lines yielded excellent Z’ ( &gt;0.5) and S:B ( &gt;30) that can support a long-term (7 day) combinatorial drug screening approach thus highlighting the impact of testing in a more complex but translationally relevant system.

Complex (not complicated) <i>in vitro</i> scale-able models for phenotypic drug screening

ACS Fall 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

Complex (not complicated) in vitro scale-able models for phenotypic drug screening