Chemotherapy has a lot of side effects, from leaving you bald to severe pain, not to mention that is not 100 % effective and recurrent cancer may still occur.

But a new research made on ovarian cancer patients undergoing chemotherapy found that those possessing a mutant disabled type of the tumor-suppressing gene p53 were twice more likely to survive than patients with the normal version of the gene. This is puzzling, as this gene is known to stop cancer in the first place.

The p53 protein goes in the body to the place where cell damage occurs, trying to freeze the cell cycle and fix the cell. When it does not succeed, it starts apoptosis (programmed cell death). "When you do chemo, we don't want cells to survive," explained lead researcher John McDonald, chair of the biology department at the Georgia Institute of Technology in Atlanta. "If you have functional p53, you may repair some of those cells subjected to chemo-and they are still cancer cells."

McDonald's team investigated the gene activity in malignant and benign tumors from ovarian cancer patients, some of them treated with chemotherapy before surgery. When the researchers looked at the tumors from those patients with pre-surgery chemotherapy, they appeared to be assigned in two groups: some displayed genes activated in a benign tumor while the others looked like they had not received chemotherapy at all. "We found that a lot of the changes in gene expression were involving genes that were in the programmed cell death pathway," says McDonald.

In the case of subjects whose tumors looked like untreated, the p53 gene was mutated, encoding a nonfunctional protein. "Normally in the literature you will see that if you have a mutation in p53, your prognosis is quite poor," McDonald notes. Despite this, five years after treatment and surgery, 70 % of the subjects carrying the mutant survived, compared to 30 % of those carrying the normal variant of the gene. "Cells are much more susceptible to DNA damage, such as chemotherapy, when they are in active division cycle," explained Yue Xiong, a professor of biochemistry and physics at the University of North Carolina at Chapel Hill. "As a result, if a cell with damaged DNA is not in active division cycle-for example, arrested by the function of p53-it would have better chance to survive the chemotherapeutic treatment than those cells that do not have p 53 function and continue to their cell cycle progression with damaged DNA."

This translates into cancer recurrence. McDonald's team shows that p53 must be turned off during chemotherapy to permit a complete clearing of malign cells. "I don't think knocking out p53 in a cancer patient is a good thing. It's just when you're doing chemotherapy", said McDonald, pointing to the tumor inhibiting qualities of this protein.