Developing new therapeutic strategies against head and neck cancer

点击翻译按钮获取中文摘要

Abstract Head and neck cancer (HNC) is the sixth most prevalent cancer in the world, and oral cancer is the most common subtype. The World Health Organization estimates ~330,000 deaths per year globally. The overall survival rate (50-60%) has not improved over the past couple of decades, despite significant improvements in surgical procedure, radiotherapy, and chemotherapy. The risk factors associated with oral cancer includes tobacco use, excessive alcohol consumption, betel quid chewing, and human papillomavirus (HPV) infection. HPV infection is likely to be reduced in the future due to successful vaccination and better prognosis. There is a critical need to define the HNC disease processes, and to identify better therapeutic strategies for successful HNC patient management. Further, non-traditional therapies must be investigated as adjuncts to reduce the risk of recurrence and improve survival. In our current funding period, we made several important novel observations. We showed that bitter melon extract feeding alters c-Met signaling and prevents HNC growth in preclinical models. We subsequently showed an immunomodulatory role of bitter melon extract, although the precise mechanism is yet to be determined. Further, we found several long non-coding RNAs are altered in feeding of bitter melon extract in a carcinogen-induced model. Very recently, we identified momordicine-I, one of the active metabolites of bitter melon, which shows therapeutic anti-tumor activity in an oral cancer preclinical model. Although we gained much evidence for bitter melon in prevention of HNC from our and other studies, considerable knowledge gaps remain in understanding the mechanism of momordicine-I on tumor metabolism and immune regulation, and its therapeutic use. Based on our and others results, we hypothesize that combining momordicine-I with other current therapeutics will improve efficacy in tumor regression. We will also examine the changes in glucose and lipid metabolism and the tumor microenvironment after treatment with momordicine-I using a mouse model. Results from this study will have important translational implications and significant benefits along with current therapy. Innovation: Our study will examine for the first time the therapeutic and mechanistic effects of momordicine-I in HNC animal models for major translational impact.