Combinatorial targeting of epigenetic mechanisms in liver cancer (C02)

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

Project C02 (Dauch/Bitzer; Combinatorial targeting of epigenetic mechanisms in liver cancer) is investigating the potential of epigenetic targeting in HCC therapy, especially combinatorial approaches to HDAC inhibition. Recently the project has demonstrated strikingly different HCC responses to different HDAC inhibitors with potent effects of Romidepsin and Panobinostat in mouse and human HCC- and ICCA-cells. Strong induction of transcription via initial transcription factors and c-MYC was contrasted by reduced transcription elongation promoting transcription/replication collision, replication stress and DNA damage resulting in apoptosis, which was accelerated and strengthened by combinatorial ATM or CHK1 inhibition. In the next funding period, the project will investigate the mechanisms and therapeutic potential of inhibition of different HDACs and adenosine receptor signalling as well as respective combinatorial treatments in different HCC/ICCA mouse models. In vivo RNAi screens will address new combinatorial epigenetic approaches to ICCA.

• 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: Professor Dr. Michael Bitzer; Dr. Daniel Dauch, Ph.D.