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Adrenocortical carcinoma is a rare cancer, with an incidence of 1-2/million. Surgical resection is the only potential for a cure at this time. However, 40-70% of cases are metastatic at the time of diagnosis, preventing complete resection and leading to a 5 year survival rate of 25-30%. The only approved chemotherapy, mitotane, is not well-tolerated by patients and shows response in only a quarter of tumors. The ACC Program began in 2006 as a collaborative effort developed through a generous donation from the Advancing Treatments for Adrenocortical Carcinoma (ATAC) Fund (www.atac.org). The program has and continues to build a repository of ACC tumors from around the world. Multiple genetic and genomic technologies available at TGen (microarray expression profiling, single nucleotide polymorphism (SNP) analysis, comparative genomic hybridization (CGH), and tissue microarray (TMA), chemical synthetic lethal screening (RNAi)) generate data from the tumors that is being analyzed both separately and in combination to elucidate the acquired genomic changes that characterize this tumor type. These insights into the cellular processes of carcinogenesis in the adrenal cortex allow the identification of novel therapeutic targets necessary in the treatment of this rare, aggressive endocrine tumor. The program is translating our expanding knowledge of the particular cellular changes in ACC into in vitro and in vivo experiments as preliminary data for clinical trials.
Additionally, the ACC data sets represent an opportunity to test various methodologies geared toward using the NCI60 cell line panel as an initial step to identifying potential therapeutic targets in other rare tumor types. The NCI60 cell line panel was developed by the Developmental Therapeutics Program of the National Cancer Institute to screen compounds for anti-cancer activity. Over 100,000 compounds have been tested so far, and the cell lines have been extensively characterized at the DNA, RNA and protein levels. Combining this data can identify associations of drug response with sets of molecular parameters that can then be verified experimentally.
Dr. Bussey received her B.S. in general biology from the University of Arizona. She received her Ph.D. in Molecular and Medical Genetics from Oregon Health Sciences University where her dissertation research focused on the cytogenetic and molecular characterization of pediatric germ cell tumors, a group of rare tumors in children. Prior to coming to TGen as an Associate Investigator and Lead Investigator for the ACC Research Program, she did a post-doctoral fellowship and worked as a contract scientist with John Weinstein, M.D., Ph.D. and the Genomics and Bioinformatics lab in the Laboratory of Molecular Pharmacology at the NCI. Her work there focused on integrative analysis of array CGH data and expression data in the NCI60 and development of computational tools to facilitate such analyses.
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