Date Published: 6 June 2011

Faults in p53 may be used to select best treatment for ovarian cancer patients

Faults in tumour suppressor protein p53 (also known as protein 53 or tumor protein 53, and encoded by the TP53 gene) could be used to predict which drug combination ovarian cancer patients are most likely to benefit from according to research reported on Sat 4 Jun 2011.


A recent study conducted by scientists at Newcastle University, the UCL Cancer Institute and the Medical Research Council (MRC) has found that women with faults in p53 were 50% less likely to survive following treatment with the drug carboplatin alone, but were more likely to benefit from the addition of the drug paclitaxel to the standard treatment of carboplatin.

Women without such mutations in p53 were found to have better survival rates overall but did not benefit from having paclitaxel added to their treatment, so could perhaps be spared unnecessary side effects in the future.

Professor Hilary Calvert, who led the study, said:

" These results show that ovarian cancer patients whose tumour had a faulty p53 gene survive longer if given paclitaxel in addition to carboplatin. Although survival rates have improved dramatically in recent years, ovarian cancer remains a deadly cancer in women and efforts to improve survival by targeting treatments at those most likely to benefit are urgently needed."

The researchers examined tumour samples from 265 patients who had taken part in the MRC's ICON 3 study, which had found no significant benefit in giving patients paclitaxel in addition to the standard treatment of carboplatin. That result had contradicted earlier studies, which had showed that adding paxlitaxel to treatment did improve survival, leading to this drug combination being adopted as a standard treatment for ovarian cancer. The scientists who conducted and interpreted this latest research explained that the difference in response to paxlitaxel could be related to the genetic makeup of the tumour which varies between patients, and suspected that p53 faults may be behind this.

To test their theory the scientists sequenced the DNA of all the tumour samples to see which had p53 faults. This revealed that p53 was inactive or faulty in around half of the samples (130/265) and also that patients only benefited from paxlitaxel if p53 was faulty in their tumour.

Dr Lesley Walker, Cancer Research UK's director of cancer information, said:

" Our scientists discovered p53 over thirty years ago and it's good to see this now being used as a biomarker to improve treatment for patients.
_ There's no such thing as a one-size-fits-all drug and increasingly scientists are developing ways to identify groups of patients that are most likely to respond to a particular drug. This approach is called stratified medicine and many scientists now believe it could transform cancer treatment in the future
."


Reference to Paper
:
Evaluation of p53 mutation as a predictive biomarker for outcome to chemotherapy in ovarian cancer, abstract number 10522, ASCO (2011).


Source: Cancer Research UK
http://www.cancerresearchuk.org

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