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An article in 'Cell' reveals a new resistance mechanism to chemotherapy in breast and ovarian cancer
Date:6/18/2013

It is estimated that between 5% and 10% of breast and ovarian cancers are familial in origin, which is to say that these tumours are attributable to inherited mutations from the parents in genes such as BRCA1 or BRCA2. In patients with these mutations, PARP inhibitors, which are currently in clinical trials, have shown encouraging results that make them a new option for personalised cancer treatment, an alternative to standard chemotherapy. Nevertheless, the latest studies indicate that a fraction of these patients generate resistance to the drug and, therefore, stop responding to the new treatment.

The team led by Spanish National Cancer Research Centre researcher scar Fernndez-Capetillo, head of the Genomic Instability Group, together with researchers from the National Cancer Institute in the US, have participated in a study that describes the causes that explain why tumours with BRCA1 and BRCA2 mutations stop responding to PARP inhibitor drugs.

"PARP inhibitors are only toxic in tumours that have an impaired DNA repair mechanism, such as those that contain BRCA1/2 mutations" says Mara Nieto-Soler, a researcher from Fernndez-Capetillo's team.

According to the researchers, the problem arises when these tumours, in addition to having BRCA1 and/or BRCA2 mutations, also contain secondary mutations in other proteins such as 53BP1 or PTIP, whose function is to restrain DNA repair. In these cases, the mutations mutually compensate for each other, the tumour cells recover the ability to repair their DNA and the drug stops working.

Fernndez-Capetillo says: "This is one of the first studies to demonstrate that secondary mutations can make tumours resistant when faced with specific treatments like, in this case, PARP inhibitors".

NEW DIAGNOSTIC TESTS WITH SECONDARY MUTATIONS

When the researchers compared different treatments, they observed that for those tumours with BRCA1 and/or BRCA2 mutations that also pres
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Centro Nacional de Investigaciones Oncologicas (CNIO)
Source:Eurekalert

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