TEAD Time: Why the Hippo-YAP/TAZ/TEAD Pathway is Having a Moment in Oncology

The Hippo pathway is a well-known regulator of tissue growth and organ size and gets its name from the Hippo kinase (Hpo in Drosophila, MST1/2 in humans), which when mutated leads to “hippopotamus”-like tissue overgrowth. Recently, industry interest in the pathway has increased thanks to several independent studies in 2023, and the field appears to be at an important inflection point for drug discovery. This target brief reviews current efforts and therapeutic hypotheses for drugging the TEAD transcription factors in cancer, including clinical molecules, paralog-selective molecules, and TEAD degraders.