Pre-existing Functional Heterogeneity of Tumorigenic Compartment as the Origin of Chemoresistance in Pancreatic Tumors

• DOI: 10.1016/j.celrep.2019.01.048
• Publication Date: 2019-02-05T16:07:04Z
• Authors: Sahil Seth; Chieh-Yuan Li; I-Lin Ho; Denise Corti; Sara Loponte; Luigi Sapio; Edoardo Del Poggetto; Er-Yen Yen; Frederick Scott R...; Michael Peoples; Tatiana Karpinets; Angela Kay Deem; Tapsi Kumar; Xingzhi Song; Shan Jiang; Ya’an Kang; Jason Fleming; Michael Kim; Jianhua Zhang; Anirban Maitra; Timothy Paul Heff...; Virginia Giuliani; Giannicola Genovese; Andrew Futreal; Giulio Francesco ...; Alessandro Carugo; Andrea Viale
• Keywords: clone (Java method)

Adaptive drug-resistance mechanisms allow human tumors to evade treatment through selection and expansion of treatment-resistant clones. Here, studying clonal evolution tumor cells derived from pancreatic tumors, we demonstrate that in vitro cultures vivo are maintained by a common set tumorigenic can be used establish replica (CRTs), large cohorts animals bearing with identical composition. Using CRTs conduct quantitative assessments adaptive responses therapeutics, uncovered multitude functionally heterogeneous subpopulations differential degrees drug sensitivity. High-throughput isolation deep characterization unique lineages showed genetic transcriptomic diversity underlying diverse subpopulations. Molecular annotation gemcitabine-naive distinct the context generated signatures predict response chemotherapy, representing potential biomarker stratify patients cancer.