Targeting the Hippo Pathway in Prostate Cancer: What's New?

Simple Summary Prostate cancer is the most commonly diagnosed cancer in men in the UK, accounting for the deaths of over 11,000 men per year. A major problem in this disease are tumours which no longer respond to available treatments. Understanding how this occurs will reveal new ways to treat these patients. In this review, the latest findings regarding a particular group of cellular factors which make up a signalling network called the Hippo pathway will be described. Accumulating evidence suggests that this network contributes to prostate cancer progression and resistance to current treatments. Identifying how this pathway can be targeted with drugs is a promising area of research to improve the treatment of prostate cancer. Identifying novel therapeutic targets for the treatment of prostate cancer (PC) remains a key area of research. With the emergence of resistance to androgen receptor (AR)-targeting therapies, other signalling pathways which crosstalk with AR signalling are important. Over recent years, evidence has accumulated for targeting the Hippo signalling pathway. Discovered in Drosophila melanogasta, the Hippo pathway plays a role in the regulation of organ size, proliferation, migration and invasion. In response to a variety of stimuli, including cell-cell contact, nutrients and stress, a kinase cascade is activated, which includes STK4/3 and LATS1/2 to inhibit the effector proteins YAP and its paralogue TAZ. Transcription by their partner transcription factors is inhibited by modulation of YAP/TAZ cellular localisation and protein turnover. Trnascriptional enhanced associate domain (TEAD) transcription factors are their classical transcriptional partner but other transcription factors, including the AR, have been shown to be modulated by YAP/TAZ. In PC, this pathway can be dysregulated by a number of mechanisms, making it attractive for therapeutic intervention. This review looks at each component of the pathway with a focus on findings from the last year and discusses what knowledge can be applied to the field of PC.