Specifically for HNSCC, our results indicate that the frequent alteration of FAT1 might result in defective Hippo signaling and unrestrained YAP1 activity, thus raising the possibility that molecular therapies targeting YAP1 or its downstream targets may represent an attractive precision medicine therapeutic option for the treatment of this and other malignancies harboring genomic alteration in the FAT family of tumor suppressor genes. Here, YAP1 is linked to head and neck squamous cell carcinoma.