Functional and genomic heterogeneity of long-term self-renewing compartment as the origin of treatment resistance in pancreatic tumors

Study ID Alternative Stable ID Type
EGAS00001003442 Other

Study Description

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

Study Datasets 1 dataset.

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Dataset ID Description Technology Samples
Whole Exome Sequencing on PDAC PDX1 parental sample and 12 clones.
Illumina HiSeq 2000 13

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