MiRCHOL SIGNED

Project "MiRCHOL" data sheet

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 Partnership

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 Project objective

Cholangiocarcinoma (CCA) is a dismal type of liver cancer which incidence has more than doubled the last 20 years and mortality rate in Europe alone increased 37%, reflecting the limited treatment options. In >70% of patients CCA is unresectable due to advanced stage of disease at diagnosis, resulting in a 5% 5-year survival rate. CCA is characterized by molecular and clinical heterogeneity, complicating therapy and assessment of drug efficacy. Tumor heterogeneity is emphasized in limited response of therapy (drug resistance) and besides genomic instability a likely consequence of deregulated pathways under control of microRNAs (miRs). Each miR can regulate multiple genes/pathways, directly linking them to tumor heterogeneity. Deregulation of miRs can cause/control chemoresistance in other cancers, but in CCA their role is yet unclear. Thus, detailed characterization of miRs in CCA, focusing on their impact in drug resistance is urgently needed. Hence, I have 3 specific aims of this proposal: to 1) characterize the deregulated expression pattern of miRs involved in CCA pathogenesis and integrate this data with transcriptomes obtained from matched patients; 2) determine the role of deregulated miRs in control of chemoresistance, and 3) modulate by genome-editing key deregulated miR(s) targeting chemoresistant genes using the novel `CRISPR-Mir’ method. Achievement of these aims will yield key new insights into the role of miRs in orchestrating CCA progression and metastasis, as well as their involvement in drug resistance. My findings will have an impact on the society and in particular in patient outcome. Dr. Andersen, a world-wide expert in the molecular pathogenesis of CCA with a vast experience in genome medicine, will supervise the project. Successful completion of this proposal will enable me to expand my scientific expertise (plus technical and transferable skills) and to establish myself as an independent researcher in hepatobiliary and translational research.