Abstract
Abstract There are currently 6 FDA approved therapies in metastatic renal cell carcinoma and their introduction has improved both time to progression and survival in these patients. Despite treatment with targeted therapies approximately 20% of patients do not respond and the remaining patients will most likely develop resistance during the first 18 months of treatment. The aim of this study was to identify a link between differences in sensitivity to targeted therapies, the vHL status and the expression of genes involved in the mTOR pathway in both historic and primary renal cancer cell lines. Drug sensitivity and gene expression data was analysed in 6 historic and 10 primary renal cancer cell lines obtained from nephrectomy specimens. Gene expression data was also available from an additional 68 renal tumours. We found that cell lines with mutated or absent vHL showed increased sensitivity to rapamycin (p<0.01) but not to other therapies. Gene expression data showed that the expression of REDD1 (regulated in development and DNA damage responses 1), a known HIF1 target gene which inhibits the mTORC1 pathway in response to hypoxic stress correlates with rapamycin sensitivity (R-squared = 0.64, p=0.05). REDD1 expression was also higher in renal tumours when compared with matched normal tissue (p<0.01) and was found to correlate with CAIX expression (R-squared = 0.47, p<0.01). CAIX expression is associated with reduced survival in renal cell carcinoma and so further analysis is being performed to establish a potential role of REDD1 as a prognostic marker. Our findings suggest that vHL status and the levels of REDD1 expression in renal cancer cell lines can predict sensitivity to rapamycin. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3942. doi:1538-7445.AM2012-3942
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