Those patients whose tumors had 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 online, peer-reviewed, 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.
Five years later, only 30 percent of the chemotherapy cancer patients clustering in the benign group were alive, while 70 percent 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.
A standard belief in cancer research is that a working p53 is essential in helping chemo patients because it turns on the killing mechanism for the cells that were damaged by chemo. But McDonald points out that p53 can also help repair damaged cells. If p53 is repairing cancer cells, that may lead to cancer recurrence."We think p53 may actually help some cancer cells make a comeback,"
McDonald and colleagues are continuing to test their theory by conducting studies in cell cultures and mice. If it bears out, then disabling the gene in tumors, through medications or new genetic techniques during chemotherapy may help patients survive.
In addition to McDonald, the research team consisted of: Benedict Benigno, gynecologic oncologist and founder of the Ovarian Cancer Institute; Lilya Matyunina, Erin B. Dickerson, Nina Schubert, and Nathan J. Bowen from Georgia Tech and the Ovarian Cancer Institute; Sanjay Logani from Emory University; and Carlos Moreno from Emory's Winship Cancer Institute.
The research was supported by the Georgia Cancer Coalition, the Georgia Tech Research Foundation, the Robinson Family Foundation and the Larry and Beth Lawrence Foundation.
Scientists spin artificial silk from whey protein
24.01.2017 | Deutsches Elektronen-Synchrotron DESY
Choreographing the microRNA-target dance
24.01.2017 | UT Southwestern Medical Center
A Swedish-German team of researchers has cleared up a key process for the artificial production of silk. With the help of the intense X-rays from DESY's...
For the first time ever, a cloud of ultra-cold atoms has been successfully created in space on board of a sounding rocket. The MAIUS mission demonstrates that quantum optical sensors can be operated even in harsh environments like space – a prerequi-site for finding answers to the most challenging questions of fundamental physics and an important innovation driver for everyday applications.
According to Albert Einstein's Equivalence Principle, all bodies are accelerated at the same rate by the Earth's gravity, regardless of their properties. This...
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
24.01.2017 | Physics and Astronomy
24.01.2017 | Life Sciences
24.01.2017 | Health and Medicine