Xiaoying Yin, MD, is working on several research projects:
1. Evaluate the anti-tumor effect of enzastaurin, a PKC-β inhibitors on HNSCC. Protein kinase C (PKC) is a family of serine/threonine kinases known to play critical roles in the signal transduction pathways involved in growth factor response, cell proliferation, differentiation, and apoptosis. Therefore, the PKCs are potential targets for cancer therapies. Enzastaurin is a specific protein kinase C beta (PKC-β) inhibitor that has been reported effective for inhibiting tumor growth in many other tumor types. In addition to specifically inhibiting tumor-derived VEGF-induced angiogenesis, it has been reported that enzastaurin can directly inhibit proliferation, and induce apoptosis which will inhibit tumor growth in vitro and in vivo. Our research project is aimed to (1) evaluate the effect of enzastaurin on HNSCC as an antitumor agent alone and as a radiosensitizer with radiation both in vitro with HNSCC cell lines and in vivo using a novel mice model that mimics the delivery of concurrent chemoradiation in HNSCC patients, (2) help unravel the mechanism of the effect of enzastaurin and cisplatin by analyzing enzastaurin/cisplatin-induced protein level changes in signal transduction pathways and gene expression changes that are due to enzastaurin/cisplatin and radiation treatment, and (3) refine this murine model of chemoradiation responsiveness for use with other novel agents.
2. Genetic study of head and neck squamous cell carcinoma (HNSCC). Working with Neil Hayes, MD, (Division of Medical Oncology) and Carol G. Shores, MD, PhD, we received a University Cancer Research Fund competitive grant for 2009-2011 for genetic study of head and neck cancer. Through the past 6 years, we have collected about 150 of HNSCCA tumors samples from patients at UNC. Using this tissue bank, we will (1) independently validate a priori two previously identified head and neck squamous cell carcinoma molecular subtypes (basal and epidermal-mesenchymal transformed) and develop an assay for clinical detection tumor molecular subtypes, (2) distinguish HNSCC subtypes and identify causative genomic aberrations (amplification and deletions) as measured by high resolution DNA copy number assays, and (3) evaluate clinical courses of HNSCC subtypes using a large population based cohort of HNSCC derived from The North Carolina Head and Neck Cancer Epidemiologic Study (CHANCE).
3. Evaluate the anti-tumor effect of Hsp90 inhibitors on HNSCC. Collaborating with Biogen Idec Corporation, we have studied a novel class of chemotherapy agents, Hsp90 inhibitors, BIIB021. Hsp90 stabilizes cellular proteins, and inhibition can lead to the degradation of several tumor related proteins, thereby interrupting several pathways simultaneously. The Hsp90 inhibitor BIIB021 has been shown to radiosensitize HNSCC in a xenograft model, with minimal side effects and disruption of the expected proteins. A paper about this research is underway.