could magnetic resonance spectroscopy be able to predict HSP90 inhibitor efficacy?

[Lani]

heat shock protein 90 inhibitors like 17 AAG have been shown to deplete her2+ breast cancer of her2 receptors and causes significant tumor regression
This study has found (in rodents) that a MRS scan could predict those tumors likely to respond to HSP90 inhibitors. They are still in clinical trials, but moving closer to approval. Anything which helps direct the trials to those in which it is most likely to be efficacious moves its approval up and helps it to be used in those likely to benefit and not in those who are not.

BMC Res Notes. 2012 May 23;5(1):250. [Epub ahead of print]
Effects of HSP90 inhibitor 17-allylamino-17- demethoxygeldanamycin (17-AAG) on NEU/HER2 overexpressing mammary tumours in MMTV-NEUNT mice monitored by Magnetic Resonance Spectroscopy.
Rodrigues LM, Chung YL, Al Saffar NM, Sharp SY, Jackson LE, Banerji U, Stubbs M, Leach MO, Griffiths JR, Workman P.
Abstract
ABSTRACT:
BACKGROUND:
The importance of ERBB2/NEU/HER2 in the response of breast tumours to the heat shock protein 90 (HSP90) inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG; tanespimycin) has been demonstrated in the clinic. ERBB2 is an oncoprotein client that is highly dependent on HSP90. This and other oncogenic client proteins (e.g. C-RAF, ALK and CDK4) are depleted by 17-AAG in both animal tumours and patients. Here we investigate by Magnetic Resonance Spectroscopy (MRS) the metabolic response of 17-AAG in spontaneous, NEU/HER2 driven mammary tumours in transgenic MMTV-NEU-NT mice and in cells isolated and cultured from these tumours.
METHODS:
Mammary tumours were monitored by 31P MRS in vivo and in tumour extracts, comparing control and 17-AAG treated mice. A cell line derived from NEU/HER2 mammary tumours was also cultured and the effect of 17-AAG was measured by 31P MRS in cell extracts. Molecular biomarkers were assessed by immunoblotting in extracts from cells and tumours. For comparison of tumour volume, metabolite concentrations and Western blot band intensities, two-tailed unpaired t-tests were used.
RESULTS:
The NEU/HER2 mammary tumours were very sensitive to 17-AAG and responded in a dosedependent manner to 3 daily doses of 20, 40 and 80mg/kg of 17-AAG, all of which caused significant regression. At the higher doses, 31P MRS of tumour extracts showed significant decreases in phosphocholine (PC) and phosphoethanolamine (PE) whereas no significant changes were seen at the 20mg/kg dose. Extracts of isolated cells cultured from the mammary carcinomas showed a significant decrease in viable cell number and total PME after 17-AAG treatment. Western blots confirmed the expected action of 17-AAG in inducing HSP72 and significantly depleting HSP90 client proteins, including NEU/HER2 both in tumours and in isolated cells.
CONCLUSIONS:
The data demonstrate the high degree of sensitivity of this clinically relevant NEU/HER2- driven tumour model to HSP90 inhibition by 17-AAG, consistent with the clinical data, and suggest that the metabolic signature of choline phospholipids obtained by MRS could be useful both as a preclinical and clinical tool for investigating surrogate markers of response to treatment.
PMID: 22621282