Functional genetic dissection of hepatocarcinogenesis in NASH (A03)

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

Project A03 (Zender; Functional genetic dissection of hepatocarcinogenesis in NASH) aims to dissect the molecular mechanisms of NASH-driven HCC and to identify novel targets to overcome the therapy resistance of NASH-driven HCC. By screening approaches it has established MKK4 as a valid target to suppress NASH-induced HCC and found ‘induced lipotoxicity’ as a new therapeutic concept for NASH-HCC. In the new funding period A03 will determine extrinsic and intrinsic mechanisms of NASH-HCC suppression by MKK4 inhibition and explore combined MKK4/MEK inhibition. The promising potential of LXRα activation will be followed by preclinical testing of LXRα agonistic compounds. Further screening approaches will address the factors mediating immune checkpoint inhibitor resistance and intrahepatic metastasis in NASH-HCC.

• 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 Heads: Dr. Ramona Rudalska, until 6/2021; Professor Dr. Lars Zender