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Patients with aberrations in two genes respond better to drugs blocking a well-known cancer pathway
Date:11/7/2012

Cancer patients with mutations or variations in two genes - PIK3CA and PTEN - who have failed to respond to several, standard treatments, respond significantly better to anti-cancer drugs that inhibit these genes' pathways of action, according to research presented at the 24th EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Dublin, Ireland, today.

Dr Filip Janku (MD, PhD), assistant professor in Investigational Cancer Therapeutics at MD Anderson Cancer Center (Houston, USA), told the meeting that mutations in PIK3CA and aberrations (loss of function or mutation) in PTEN were present in a wide range of tumours and were thought to be involved in the development of cancer. These genes act via a pathway known as the PI3K/AKT/mTOR pathway, and so inhibiting the pathway could improve the patients' response to treatment.

The researchers tested 1656 patients with a variety of cancers and found that 146 (9%) had PIK3CA mutations, 150 (13%) had PTEN aberrations and 14 (1%) had both.

They treated 134 of the patients who had PIK3CA mutations, PTEN aberrations or both in early-phase clinical trials that included drugs that block the PI3K/AKT/mTOR pathway. The patients had failed an average of three, previous treatments. Of these patients, 107 were also tested for mutations in another, known cancer-causing gene, KRAS.

Dr Janku said: "We found that heavily pre-treated patients with PIK3CA mutations, PTEN aberrations, or both had a significantly higher response rate on protocols incorporating PI3K/AKT/mTOR inhibitors compared to patients without known PIK3CA/PTEN aberrations treated on the same protocols. In addition, we noticed that patients who had these and also simultaneous mutation in codons 12 or 13 of KRAS (which is a likely mechanism of drug resistance) did not respond to protocols with PI3K/AKT/mTOR inhibitors.

"Furthermore, it looks as if treatment with a single agent may not be sufficient, as
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Contact: Emma Mason
wordmason@mac.com
ECCO-the European CanCer Organisation
Source:Eurekalert

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