The Hippo/YAP1 signaling mediators of tumor initiation and therapeutic target in human papillomavirus-positive head and neck cancer

Head and neck cancer (HNC) is a prevalent malignancy, with approximately half a million new cases diagnosed worldwide each year. In the last three decades, the number of patients diagnosed as suffering from human papillomavirus-induced HNC (HPV-HNC) has increased dramatically. Although these patients respond relatively well to therapy, 35% of them will die from their HPV-HNC. There is therefore an unmet need to develop more effective therapies for patients with HPV-HNC.

To develop and investigate new anti-HPV-HNC treatments, we will first understand how HPV alters the signaling machinery in normal cells to transform into aggressive malignant cells, and then we will test if blocking such signaling machinery reduces disease initiation and progression. Our research proposal aims to uncover how HPV genes activate the Hippo/YAP1 signaling pathway and to test the efficacy of YAP1 inhibitors in preventing HPV-HNC initiation and halting the progression of existing HPV-HNC tumor. We envision that our research will shed light on the biology of HPV-induced HNC, and the findings will be translated in the upcoming years for treating HPV-HNC patients.