YES-ASSOCIATED PROTEIN (YAP) – A PROMISING THERAPEUTIC TARGET FOR HEPATOCELLULAR CARCINOMA
Hepatocellular carcinoma (HCC), the third leading cause of cancer mortality, carries a dismal prognosis and represents a major health problem. A better understanding of the molecular pathways involved in HCC development may represent an important approach for the improvement o f the therapeutic strategies for this cancer. The Hippo signalling pathway, a growth suppressive mechanism that antagonizes the transcriptional co-activator Yes-associated protein (YAP), has been recently found altered in human HCC. Moreover, using the Resistant-Hepatocyte (R-H) rat model, recently published data established that the Hippo pathway deregulation occurs already at the early stages of HCC development, making this pathway an important therapeutic target. Many strategies have been proposed to mod ulate the activity of the Hippo pathway, and in particular that of the final effector YAP, most of which require complex gene manipulations, useful to understand the functions of the pathway but difficult to apply on patients. One of the few drugs able to inhibit in vivo the pro-carcinogenic effect of YAP activation is verteporfin, which disrupts the formation of the complex between YAP and the TEAD transcription factors, causing a significant reduction of the number and size of preneoplastic foci induced in rats liver by R-H protocol. In this review, we give a short summary of Hippo pathway, providing the evidences of its deregulation in mouse, rat and human liver cancer and discuss the possibility to treat HCC with new drugs targeting the transcriptional co-activator YAP