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GEN News Highlights : May 16, 2007

p53 May Help Cancer Thrive

Researchers found that patients with the nonfunctional version of the protein respond better to chemotherapy.

A gene thought to be essential in helping chemotherapy kill cancer cells may actually help them thrive. In a new study of chemo patients, scientists at the Georgia Institute of Technology and the Ovarian Cancer Institute found that subjects whose tumors had mutations in the gene p53 had a better chance of survival compared to patients with normal p53.

When a cell is malfunctioning or injured, the gene p53 comes in and tries to repair the cell. If the cell can't be repaired, p53 starts apoptosis. p53 has been thought to assist in killing the cancerous cells that the chemotherapy treatment injures.

In the study, researchers took malignant and benign ovarian tumors straight from the operating room and compared their gene-expression profiles. Some of the cancer patients had been treated with chemotherapy prior to surgery and some had not. At this point, researchers didn't consider whether the patients actually had malignant tumors or had been treated with chemotherapy. However, they found that the gene-expression profiles of the tumors clustered the chemotherapy-treated patients into two groups: those whose profiles were similar to cancer patients who had not been treated with chemo and those whose profiles were similar to patients with benign tumors.

As they continued their analysis, they found that the main difference between the groups' genetic profiles was the gene p53. While both groups had roughly the same amount of the protein encoded by p53, the cancer group had mutations in their p53 that caused the gene’s corresponding protein not to function. The benign group's p53 was normal.

Five years later, only 30% of the chemotherapy cancer patients clustering in the benign group were alive, while 70% of those clustering in the cancer group were still alive. The stage of cancer at the time of surgery had no correlation to who survived and who didn't. What did seem to have an effect was whether p53 was working or not in the chemotherapy-treated tumors.

The results appear in the May 16 edition of PLoS ONE.