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UK study uncovers clue to cancer drug resistance

Wednesday 13 February 2008

A new study jointly funded by Breakthrough Breast Cancer and Cancer Research UK has revealed how cancer cells carrying a faulty gene can become resistant to treatment.

Drug resistance is one of the major reasons for treatment failure, and the finding could potentially lead to new treatments that make resistant cancer cells sensitive to treatment once more.

Researchers at the Breakthrough Breast Cancer Research Centre in London conducted studies on cancer cells containing a faulty version of the gene BRCA2, which is involved in repairing damaged DNA. Cells containing faults in this gene accumulate even more genetic damage as they grow and multiply.

Ironically, this also renders them extremely sensitive, at least initially, to cancer drugs that damage DNA, such as PARP inhibitors and carboplatin.

But BRCA2 cancers can quickly become resistant to these therapies.

So the researchers looked at the state of the BRCA2 gene in cells that had become resistant. They found that the BRCA2 gene had re-activated itself, allowing the cancer to repair its damaged DNA and survive.

Professor Ashworth explained: "This genetic mechanism works like Charles Darwin's natural selection theory - it allows cancer cells to survive by changing the way treatments affect them. By understanding this process we can alter patient treatment to counter the problem of resistance.

"Drug resistance is a problem common to all types of cancer, yet this important process is poorly understood.

"Our work has shown how this occurs in some women with cancer and in the future we hope to be able to use this information to predict whether cancer patients will benefit from particular treatments. Furthermore, this information will help us to develop ways of countering the problem of resistance."

Professor Herbie Newell, Cancer Research UK's executive director of translational research, commented: "This research deepens our understanding of why some breast cancer patients with a faulty BRCA2 gene may stop responding to treatment.

"This type of research is becoming increasingly important as we seek to tailor cancer therapies to individual patients. Although at an early stage, this research may ensure that women are spared unnecessary treatment."

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