RT Journal Article SR Electronic T1 Tissue specificity of in vitro drug sensitivity JF bioRxiv FD Cold Spring Harbor Laboratory SP 085357 DO 10.1101/085357 A1 Fupan Yao A1 Seyed Ali Madani Tonekaboni A1 Zhaleh Safikhani A1 Petr Smirnov A1 Nehme El-Hachem A1 Mark Freeman A1 Venkata Satya Kumar Manem A1 Benjamin Haibe-Kains YR 2016 UL http://biorxiv.org/content/early/2016/11/03/085357.abstract AB Research in oncology traditionally focuses on specific tissue type from which the cancer develops. However, advances in high-throughput molecular profiling technologies have enabled the comprehensive characterization of molecular aberrations in multiple cancer types. It was hoped that these large-scale datasets would provide the foundation for a paradigm shift in oncology which would see tumors being classified by their molecular profiles rather than tissue types, but tumors with similar genomic aberrations may respond differently to targeted therapies depending on their tissue of origin. There is therefore a need to reassess the potential association between pharmacological response and tissue of origin for therapeutic drugs, and to test how these associations translate from preclinical to clinical settings.In this paper, we investigate the tissue specificity of drug sensitivities in large-scale pharmacological studies and compare these associations to those found in clinical trial descriptions. Our meta-analysis of the four largest in vitro drug screening datasets indicates that tissue of origin is strongly associated with drug response. We identify novel tissue-drug associations, which may present exciting new avenues for drug repurposing. One caveat is that the vast majority of the significant associations found in preclinical settings do not concur with clinical observations. Accordingly, our results call for more testing to find the root cause of the discrepancies between preclinical and clinical observations.