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The Association of PI3 Kinase Signaling and Chemoresistance in Advanced Ovarian Cancer

Carden, C. P., Stewart, A., Thavasu, P., Kipps, E., Pope, L., Crespo, M., Miranda, S., Attard, G., Garrett, Michelle D., Clarke, P. A., and others. (2012) The Association of PI3 Kinase Signaling and Chemoresistance in Advanced Ovarian Cancer. Molecular Cancer Therapeutics, 11 (7). pp. 1609-1617. ISSN 1535-7163. (doi:10.1158/1535-7163.MCT-11-0996) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://doi.org/10.1158/1535-7163.MCT-11-0996

Abstract

Evidence that the phosphoinositide 3-kinase (PI3K) pathway is deregulated in ovarian cancer is largely based on the analysis of surgical specimens sampled at diagnosis and may not reflect the biology of advanced ovarian cancer. We aimed to investigate PI3K signaling in cancer cells isolated from patients with advanced ovarian cancer. Ascites samples were analyzed from 88 patients, of whom 61 received further treatment. Cancer cells were immunomagnetically separated from ascites, and the signaling output of the PI3K pathway was studied by quantifying p-AKT, p-p70S6K, and p-GSK3? by ELISA. Relevant oncogenes, such as PIK3CA and AKT, were sequenced by PCR-amplified mass spectroscopy detection methods. In addition, PIK3CA and AKT2 amplifications and PTEN deletions were analyzed by FISH. p-p70S6K levels were significantly higher in cells from 37 of 61 patients who did not respond to subsequent chemotherapy (0.7184 vs. 0.3496; P = 0.0100), and this difference was greater in patients who had not received previous chemotherapy. PIK3CA and AKT mutations were present in 5% and 0% of samples, respectively. Amplification of PIK3CA and AKT2 and deletion of PTEN was seen in 10%, 10%, and 27% of samples, respectively. Mutations of PIK3CA and amplification of PIK3CA/AKT2 or deletion of PTEN did not correlate with levels of p-AKT, p-p70S6K, and p-GSK3?. In patients with advanced ovarian cancer, there is an association between levels of p-p70S6K and response to subsequent chemotherapy. There is no clear evidence that this is driven specifically by PIK3CA or AKT mutations or by amplifications or deletion of PTEN.

Item Type: Article
DOI/Identification number: 10.1158/1535-7163.MCT-11-0996
Subjects: Q Science
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Michelle Garrett
Date Deposited: 11 Nov 2016 10:39 UTC
Last Modified: 29 May 2019 18:10 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/58563 (The current URI for this page, for reference purposes)
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