Abstract

The HIPPO signaling pathway is an evolutionary conserved pathway that has received increasing attention in cancer research over the past years. The deregulation of HIPPO kinase signaling and the subsequent activation of the YAP1 transcriptional regulator drives tumor cell proliferation, protects from therapy by promoting cell survival and signals towards a tumor permissive immune environment. In this presentation, I will speak about how to detect YAP1 activation and will present examples of tumors with high YAP1 activity and deregulated HIPPO kinase signaling. I will further give you an overview on strategies for targeting the HIPPO-YAP1 pathway in cancer therapy, including recent advancements on small molecule allosteric ligands of TEAD proteins, which are the preferred transcription factor binding partners of YAP1 and represent the most terminal effectors of the HIPPO-YAP1 signaling cascade.