mini-liver SCCS · Human “mini-liver” stem cell culture systems: from mechanisms behind liver cancer origin and recurrence to new therapeutic treatments

Human “mini-liver” stem cell culture systems: from mechanisms behind liver cancer origin and recurrence to new therapeutic treatments

CONTEXT AND OVERALL OBJECTIVES OF THE PROJECT Primary liver cancers (PLC) are among the most lethal and prevalent cancers in the human population. Despite their significance, there is only an elemental understanding of PLC pathogenesis, notably due to a lack of models that faithfully recapitulate an original tumor. Indeed, the majority of the existing animal models (from dog to rodent) do not replicate the human disease and existing cell lines do not mimic the complex genetic spectra of these tumors. Therefore, developing a physiologically relevant in vitro cancer model to study the mechanisms behind this disease is of capital importance to facilitate finding new relevant therapeutic treatments for this disease and improve patient care. Here, we aimed at translating organoid technology to establish and characterize physiologically relevant 3D-liver models and use them to increase our understanding of the mechanisms behind PLC with the final goal to develop new anti-cancer strategies. OVERVIEW OF THE PROJECT RESULTS Thanks to the H2020-MSCA-IF fellowship I have pioneered the technique of generating organoids from PLC biopsies (so-called tumoroids) and demonstrated that they faithfully recapitulate and maintain the histopathology and genetic profile of the original tumor, even after long term culture. Therefore, they provide an extremely powerful resource for analysing the biology of PLC and develop new therapeutic strategies. Moreover, I have evaluated tumoroids use as a drug screening platform and provided the proof-of-concept that PLC tumoroids are relevant for in vitro and in vivo drug testing and for identification of actionable therapeutic targets. The outcomes of this research have the potential to significantly impact on the liver cancer research field and might facilitate finding new therapeutic treatments for this disease.

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