In a new study funded by Breakthrough Breast Cancer and Cancer Research UK, researchers examined cancer cells which contained a faulty version of the gene BRCA2.
Women who inherit this faulty gene are at a much higher risk of developing breast and ovarian cancer.
BRCA2 is involved in repairing damaged DNA but cells containing faults in this gene accumulate even more genetic damage as they grow and multiply.
It is this feature which renders them extremely sensitive to cancer drugs that damage DNA, such as PARP inhibitors and carboplatin; BRCA2 cancers can become resistant to these therapies very quickly and is one of the main reasons why treatment fails.
When the research team examined the condition of the BRCA2 gene in cells that had become resistant, they found that the BRCA2 gene had re-activated itself and this in turn allowed the cancer to repair its damaged DNA and survive.
The researchers believe their discovery could lead to new treatments that make resistant cancer cells sensitive to treatment once more.
Professor Alan Ashworth from Breakthrough Breast Cancer says this genetic mechanism allows cancer cells to survive by changing the way treatments affect them.
Professor Herbie Newell, the executive director of translational research for Cancer Research UK, says drug resistance is a problem common to all types of cancer which is poorly understood and by understanding this process patient treatment can altered to counteract the problem of resistance.
The researchers believe this particular mechanism of resistance might be a common way by which many other types of cancer become resistant to treatment.
The Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research is Europe's leading cancer research centre.
The researchers used microarray analysis to study gene expression patterns in infection-fighting white blood cells contained in the blood samples. They found alterations in the activity of 85 genes some 24 to 72 hours before diagnosis of pneumonia by the physician attending in the ICU.
"This suggests that we could start patients on antibiotics earlier, say at the first change in these genomic vital signs, and we likely could significantly improve their ability to recover from pneumonia," Cobb says.
Many of the genes identified by the research team regulate specialized immune cells known as neutrophils. These cells dramatically increase in number as bacteria invade the body. "We found genes that control neutrophil activation were turned on, and that is consistent with someone developing a bacterial infection," Cobb explains. "We did not find neutrophil genes being activated in patients who did not have infection, even though they had fevers and high white blood cell counts."
Other genes of interest regulated messenger proteins called chemokines, which send signals recruiting immune cells to fight off infection.
The scientists confirmed the ability of their genomic analysis to diagnose infection and monitor recovery in a second small group of seven patients on mechanical ventilators, two of whom developed pneumonia. As the patients healed, alterations in the expression of the 85 genes diminished, indicating that they had returned to a healthy state.
"This innovative approach has the potential to benefit patients through earlier diagnosis and treatment, and could help hospitals better control outbreaks of pneumonia in patients on ventilator support," says Sarah Dunsmore, Ph.D., who oversees sepsis grants at the National Institute of General Medical Sciences, which partially funded the study. "Dr. Cobb's long-term goal is to develop an objective way to diagnose ventilator associated-pneumonia in intensive care units and predict patients' recovery."
Cobb says he and his team now plan to evaluate the clinical usefulness of the genetic analysis in a larger, independent group of patients with ventilator-associated pneumonia.
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