Treatment of liver cancer by inducing critical transcriptional stress in cancer cells

01.07.2026 bis 30.06.2028

Primary liver cancer is the third most common cause of cancer-related deaths worldwide and novel concepts for the treatment of liver cancer patients are urgently needed.
We here established a novel strategy for the treatment of liver cancer, that is based on the induction of critical transcriptional stress in cancer cells. Overactivation of transcription by chromatin modifications triggers critical transcription-replication collisions, leading to replicative stress, DNA damage and cancer cell death. This approach shows promising therapeutic effects, but cancer cells counteract activation of transcription by reducing transcription elongation. This suggests that reactivating transcription elongation will further improve the potential of this therapeutic strategy.
With this proposal, we want to enhance the therapeutic concept of inducing transcriptional stress in cancer cells. We will further investigate this therapeutic approach and develop strategies to intensify critical transcriptional stress in cancer. Thus, we will combine chromatin modifications with an overactivation of transcription elongation or inhibition of the DNA damage response. These experiments will allow us to establish a novel therapeutic strategy for the treatment of cancer patients in the future and to identify the best target for a subsequent drug development program.