Nada M.S. Al-Saffar1, Laura L. Jackson1, Swee Sharp2, Loreta Rodrigues3, John R. Griffiths3, Paul Workman2, Martin O. Leach1
1CR-UK and EPSRC Cancer Imaging Centre, Institute of Cancer Research, Sutton, Surrey, United Kingdom; 2CR-UK Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, Surrey, United Kingdom; 3CR-UK Cambridge Research Institute, Cambridge, United Kingdom
17-AAG is a novel anticancer drug that inhibits heat shock protein 90 (HSP90) leading to combinatorial degradation of many oncogenic client proteins including NEU/HER2 and its downstream proteins, which have key roles in cell growth and survival. NEU/HER2 is overexpressed in 25% of human breast cancers. In this study, we have used 1H and 31P-MRS to establish biomarkers for HSP90 inhibition in cells isolated from a NEU/HER2-driven mammary carcinoma Oncomouse. We report a 2-fold increase in choline-containing metabolites which was associated with a decrease in NEU/HER2 expression. Hence these MRS changes could serve as biomarkers for HSP90 inhibition in cells/tumors driven by NEU/HER2.