Open AccessScreening drug effects in patient‐derived cancer cells links organoid responses to genome alterations
Author(s) -
Jabs Julia,
Zickgraf Franziska M,
Park Jeongbin,
Wagner Steve,
Jiang Xiaoqi,
Jechow Katharina,
Kleinheinz Kortine,
Toprak Umut H,
Schneider Marc A,
Meister Michael,
Spaich Saskia,
Sütterlin Marc,
Schlesner Matthias,
Trumpp Andreas,
Sprick Martin,
Eils Roland,
Conrad Christian
Publication year - 2017
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20177697
Subject(s) - organoid , biology , genome , drug response , drug , cancer drugs , cancer , computational biology , genetics , gene , pharmacology
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, matrix‐dependent 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.