Optimization and evaluation of c-myc – directed liver cancer therapy (C01)

• Subject Area: Gastroenterology
• Term: from 2017 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 314905040

Project C01 (Vogel; Optimization and evaluation of c-myc-directed liver cancer therapy) is studying the role of c-MYC in hepatocarcinogenesis with strong emphasis on clinical translation. In the first funding period the project demonstrated the context specific role of endogenous c-myc in two different murine mouse models. Contrary to the expectation liver injury was increased in cholestatic injury model and tumor development was significantly accelerated in the absence of c-myc. In the new funding period the focus will be on the immunomodulatory role of c-MYC in murine and human HCCs. Based on the recent observations of an immune-evasive role of c-MYC in several cancers and the regulatory role of CTNNB1 on c-MYC the project will investigate the influence of c-MYC on the immune contexture first using genetically defined mouse HCC models; the influence of c-MYC on immune checkpoints and immune regulators will be determined using single cell sequencing approaches; in a next step these data will we tested in human HCCs by analysing the spatial composition of the immune response, as determined by multispectral-imaging, and response to therapy in a well annotated retrospective HCC resection collective as well as investigator-initiated clinical trial cohorts using checkpoint inhibitors in HCCs.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 209: Liver Cancer - New mechanistic and therapeutic concepts in a solid tumor model
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Project Head: Professor Dr. Arndt Vogel