Head and neck squamous cell carcinoma (HNSCC) is the 5th most common cancer worldwide with 200,000 deaths annually. In the US, about 11,000 people die and 40,000 new cases are diagnosed every year. Improvements in surgery and chemoradiation have resulted in modest improvement in the 5-year survival of HNSCC; 48% survival for individuals with locally advanced disease and 26% survival for individuals with metastatic disease. A better understanding of HNSCC at the cellular and molecular level could guide development and use of new therapeutic interventions.
Epidermal Growth Factor Receptor (EGFR) belongs to the ErbB receptor tyrosine kinase family and is vital to control cell proliferation, differentiation, and homeostasis. Deregulation of EGFR impacts a considerable proportion of tumors, including head and neck, lung, colon, and breast cancer. The elevated expression and over-activation of EGFR correlate with cancer metastasis, recurrence, and poor patient prognosis.
Cetuximab, a monoclonal anti-EGFR antibody blocks EGFR activation, and has been approved by FDA to treat HNSCC. However, patients’ response rate is limited and they rapidly develop resistance to the therapy. New treatments are required to improve patient treatment outcomes.
Dr Sun has identified a new signaling pathway involving an enzyme PIPKIgi5, Mig6 a known tumor suppressor protein and LAPTM4B an oncoprotein that regulate EGFR signaling. By studying this regulatory pathway Dr Sun and his group want to understand how this pathway controls disease progression.
The long terms goals of this research are twofold. Dr Sun hopes that by understanding this pathway better it will be possible to tailor cancer therapies to individual HNSCC patients by identifying those individuals who will respond well to known treatments such as cetuximab. For those patients who will not respond well to known therapies, the signaling pathway identified provides a new target to design new drug interventions to be used alongside or as an alternative to current therapeutic intervention.