Candidate: The proposed research will develop a microarray based assay to predict the prognosis and response to treatment of primary head and neck squamous cell carcinomas (HNSCC). Dr Shores will utilize the training time provided by this grant to develop the necessary skills to translate her background in protein biochemistry to a strong base in molecular genetics. Dr Shores' career goal is to provide excellent patient care in an academic setting while developing clinical/translational cancer research. Her primary research interest is to develop novel diagnostic and treatment modalities for head and neck squamous cell carcinoma. The long term goal is to biopsy the primary tumor at first patient presentation and based on molecular analysis of the tumor, predict how aggressive the tumor will be and which treatment modality it will best respond to. Funding of this proposal will ensure that 75% of Dr Shores' time will be devoted to the proposed research project. Environment: Support for this proposal comes from the UNC Lineberger Comprehensive Cancer Center (LCCC), the Division of Otolaryngology/Head and Neck Surgery, the UNC Genomics Core Facility and the UNC Center for BioInformatics. Dr Shores is provided space in the lab of her collaborator, Dr Wendell Yarbrough, in the LCCC. All of the core facilities of the LCCC will be available for this research project. Support will include equipment, reagents and consumables for the project. Research: A microarray of genes will be assembled for this proposal. They will include genes shown to predict aggressiveness of HNSCC and all of the known genes in the DNA damage response, p53, Rb and apoptosis pathways. Sensitivity of HNSCC cell lines to cisplatin and gamma radiation will be correlated with the changes in array pattern before and after these treatments. The cell will be grown in raft cultures, a three dimensional model system of mucosal tumors. Primary HNSCC tumors will then be collected and RNA isolated for gene expression determined by the microarray. The same cells will be place in raft culture, and treated with and without cisplatin or gamma radiation. RNA will be isolated from the cultured cells, and analyzed using the microarray. Patients will be followed for initial and long term response to therapy. Gene expression patterns will be analyzed, with the goal of predicting response to therapy. In addition, microarray analysis will shed light on the molecular basis of cisplatin and radiation resistance in HNSCC. The arrays will also shed light on the molecular mechanism of resistance to therapy and control of apoptosis.
| Yin, Xiaoying; Zhang, Hong; Burrows, Francis et al. (2005) Potent activity of a novel dimeric heat shock protein 90 inhibitor against head and neck squamous cell carcinoma in vitro and in vivo. Clin Cancer Res 11:3889-96 |
