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 70 percent of subjects whose tumors had mutations in the gene p53 were still alive after five years. Patients with normal p53 displayed only a 30 percent survival rate. The findings raise the possibility of a new strategy for fighting cancer - namely, developing drugs to disable the functioning of this gene in the tumors of patients undergoing chemotherapy. The results appear in the May 16 edition of the open access journal PLoS ONE.
"P53 has long been recognized as a key player in directing chemotherapy-damaged cancer cells to self annihilate, but less attention has been paid to p53's role in repairing damaged cells,'said John McDonald, chair of Georgia Tech's School of Biology and chief research scientist at the Ovarian Cancer Institute.
When a cell is malfunctioning or injured, the gene p53 is called into action and tries to repair the cell. If the cell can't be repaired, p53 starts a process known as apoptosis that kills the cell. It's p53's role as one of the genes involved in initiating cell death that has led cancer researchers to long believe that the gene is essential to successful chemotherapy. The idea is that p53 assists in killing the cancerous cells that the chemo treatment injures.
But in this latest trial, Georgia Tech researchers found that p53 may be a ,double-edged sword." Chemotherapy patients whose tumors had a mutated p53 gene that didn't work had a much better survival rate than those who had normal p53.
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.