Deciphering the crosstalk between cancer stem cells-tumor microenvironment and therapeutic implications in intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is the second primary malignancy of the liver with few therapeutic options, late diagnosis, chemotherapy resistance and dismal prognosis. iCCA incidence and mortality increased worldwide in the last decades, linked to the rise of risk factors including non-alcoholic steatohepatitis. iCCA is a highly heterogeneous tumor characterized by a complex and dynamic tumor microenvironment (TME) where stromal cells coexist with cancer and cancer stem cells (CSC).

CSCs are a heterogeneous subpopulation of cancer cells capable of tumor initiation, malignant growth and responsible for chemoresistance.

The main objective of the “SteMiCCA” project is to identify and target the unexplored CSC-TME interactions in iCCA, aimed to better understand the complex biology and to identify new therapeutic targets for this deadly disease.

To achieve this objective, an interdisciplinary approach including in vitro (spheroids and organoids from human and mouse) and in vivo (ICC-models, subcutaneous and xenograft tumor induction) systems; high throughput transcriptomics (scRNA-Seq and RNA-Seq) and bioinformatics will be employed.

Considering my strong background and experience in iCCA and TME, and the host institution’s well-recognized expertise in stem cell biology and liver cell plasticity, this proposal envisions a successful reciprocal transfer of knowledge.

Moreover, this fellowship will allow me to gain expertise in supervision, intellectual property management, research funding and proposal writing, with the main goal to acquire more competences and reach professional maturity to start my own research line in iCCA.

This will also be a first step to strengthen my network and start contributing to European actions such as ESCALON PROJECT 825510 and EURO-CHOLANGIO-NET, created to boost multidisciplinary studies with interest in basic, translational and clinical research in the field of CCA.