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.
Keywords