The association of PI3 kinase signalling and chemo-resistance in advanced ovarian cancer
Mené sur des cellules isolées à partir d'échantillons prélevés sur des patientes atteintes d'un cancer avancé de l'ovaire, cette étude évalue l'association entre des anomalies relatives à la voie de signalisation PI3K et la résistance thérapeutique
Evidence that the phosphatidylinositide-3-kinase (PI3K) pathway is deregulated in ovarian cancer is largely based on analysis of surgical specimens sampled at diagnosis and may not reflect the biology of advanced ovarian cancer. We aimed to investigate PI3K signalling in cancer cells isolated from patients with advanced ovarian cancer. Ascites samples were analysed from 88 patients, of whom 61 received further treatment. Cancer cells were immunomagnetically separated from ascites and the signalling output of the PI3K pathway was studied by quantifying p-AKT, p-p70S6K and p-GSK3β 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 analysed by fluorescent-in-situ hybridization. p-p70S6K levels were significantly higher in cells from 37/61 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-GSK3β. 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 amplifications or deletion of PTEN.
http://mct.aacrjournals.org/content/early/2012/05/03/1535-7163.MCT-11-0996.abstract