TY - JOUR T1 - Resolving drug effects in patient-derived cancer cells links organoid responses to genome alterations JF - bioRxiv DO - 10.1101/124446 SP - 124446 AU - Julia Neugebauer AU - Franziska M. Zickgraf AU - Jeongbin Park AU - Steve Wagner AU - Xiaoqi Jiang AU - Katharina Jechow AU - Kortine Kleinheinz AU - Umut H. Toprak AU - Marc A. Schneider AU - Michael Meister AU - Saskia Spaich AU - Marc Sütterlin AU - Matthias Schlesner AU - Andreas Trumpp AU - Martin Sprick AU - Roland Eils AU - Christian Conrad Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/06/124446.abstract N2 - Cancer drug screening in patient-derived cells holds great promise for personalized oncology and drug discovery but lacks standardization. Whether cells are cultured as conventional monolayer or advanced organoid cultures influences drug effects and thereby drug selection and clinical success. To precisely compare drug profiles in differently cultured primary cells, we developed DeathPro, an automated microscopy-based assay to resolve drug-induced cell death and proliferation inhibition. Using DeathPro, we screened cells from ovarian cancer patients in monolayer or organoid culture with clinically relevant drugs. Drug-induced growth arrest and efficacy of cytostatic drugs differed between the two culture systems. Interestingly, drug effects in organoids were more diverse and had lower therapeutic potential. Genomic analysis revealed novel links between drug sensitivity and DNA repair deficiency in organoids that were undetectable in monolayers. Thus, our results highlight the dependency of cytostatic drugs and pharmacogenomic associations on culture systems, and guide culture selection for drug tests. ER -