(Press-News.org) A new tool to observe cell behavior has revealed surprising clues about how cancer cells respond to therapy – and may offer a way to further refine personalized cancer treatments.
The approach, developed by investigators at Vanderbilt-Ingram Cancer Center, shows that erlotinib – a targeted therapy that acts on a growth factor receptor mutated in some lung, brain and other cancers – doesn't simply kill tumor cells as was previously assumed. The drug also causes some tumor cells to go into a non-dividing (quiescent) state or to slow down their rate of division. This variability in cell response to the drug may be involved in cancer recurrence and drug resistance, the authors suggest.
The new tool, reported Aug. 12 in Nature Methods, may offer ways to improve personalized cancer therapy by predicting tumor response and testing combinations of targeted therapies in an individual patient's tumor.
In the personalized approach to cancer treatment, a patient's tumor is analyzed for a set of mutations to which there are matching drugs that act on those mutations.
This approach has worked rather well for many cancers that carry specific mutations, said senior author Vito Quaranta, M.D., professor of Cancer Biology.
"The genetics is well understood, the clinical effect is understood and the chemistry behind the therapy is understood. But there is a missing piece," said Quaranta. "Believe it or not, what is actually not understood is how cells respond to these drugs, what is actually happening."
The prevailing view has been that targeted therapies kill all the cells harboring a particular mutation.
But even if the tumor is composed entirely of genetically identical cells – which is unlikely – a drug will not affect all cells the same way, Quaranta explained.
"Some of these cells may die, some may just stop dividing and sit there (called quiescence), and some may keep dividing, but more slowly."
However, no current tests can provide an accurate, detailed picture of cell behavior needed to understand tumor response to drugs.
So, the investigators, led by first author Darren Tyson, Ph.D., research assistant professor of Cancer Biology, combined powerful automated, time-lapse microscopy with analytical tools and software they developed.
Using these techniques, they could capture the behavior of lung cancer cells every six to 10 minutes for up to 10 days.
As they expected, the targeted therapy erlotinib killed some cells, while others became quiescent. They observed that the drug even affected genetically identical cells (cells that arose from the same parental cell) differently.
"These cells are clearly genetically identical, as identical as they can possibly be because one cell just divided into two, but you get completely different responses: one dies and the other one doesn't," said Tyson. "This suggests that there are other things besides genetics that have to be taken into account."
What those other factors are remains unclear, but the investigators are conducting follow- up experiments to determine what might underlie this differential response.
"And presumably, it is those (quiescent) cells that ultimately result in tumor recurrence," said Tyson.
Quaranta and colleagues hope to take the technology into small clinical trials to test whether it can predict a patient's response to therapy.
"We think that we might be able to forecast what the response is going to be," Quaranta said. "We can take samples from the tumor, subject them to this assay, and since we're looking at response over time, we will have a rate of response."
This could tell oncologists how long a patient's tumor will respond to a given therapy before it recurs. Such information could also help determine which patients will require more aggressive treatment – and Quaranta believes the assay will be able to test combinations of drugs on a patient's tumor cells to find the right combination to induce a response.
"We're hoping that this assay – or some implementation of this assay – will eventually work like a personalized clinical trial," Quaranta said.
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Graduate student Peter Frick and data analyst Shawn Garbett were co-authors on the paper. The research was supported by a grant from the National Institutes of Health/ National Cancer Institute Integrative Cancer Biology Program (CA113007).
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Irvine, Calif., Aug. 10, 2012 – Gamma-ray photons seen emanating from the center of the Milky Way galaxy are consistent with the intriguing possibility that dark-matter particles are annihilating each other in space, according to research submitted by UC Irvine astrophysicists to the American Physical Society journal Physical Review D.
Kevork Abazajian, assistant professor, and Manoj Kaplinghat, associate professor, of the Department of Physics & Astronomy analyzed data collected between August 2008 and June 2012 from NASA's Fermi Gamma-ray Space Telescope orbiting Earth. ...
A targeted approach to treating toxoplasmosis, a parasitic disease, shows early promise in test-tube and animal studies, where it prevented the parasites from making selected proteins. When tested in newly infected mice, it reduced the number of viable parasites by more than 90 percent, researchers from the University of Chicago Medicine report in the Proceedings of the National Academy of Sciences.
This precisely focused therapy combines short strands of "antisense" nucleic acid-like material with a small peptide that can transport those strands through cell membranes ...
Newly published research led by Dr. David Spence of Western University, Canada, shows that eating egg yolks accelerates atherosclerosis in a manner similar to smoking cigarettes. Surveying more than 1200 patients, Dr. Spence found regular consumption of egg yolks is about two-thirds as bad as smoking when it comes to increased build-up of carotid plaque, a risk factor for stroke and heart attack. The research is published online in the journal Atherosclerosis.
Atherosclerosis, also called coronary artery disease, is a disorder of the arteries where plaques, aggravated ...
ARGONNE, Ill. (August 12, 2012) -- For the first time X-ray scientists have combined high-resolution imaging with 3-D viewing of the surface layer of material using X-ray vision in a way that does not damage the sample.
This new technique expands the range of X-ray research possible for biology and many aspects of nanotechnology, particularly nanofilms, photonics, and micro- and nano-electronics. This new technique also reduces "guesswork" by eliminating the need for modeling-dependent structural simulation often used in X-ray analysis.
Scientists from the Advanced ...
(SACRAMENTO, Calif.) — A team of investigators from UC Davis and Peking University have discovered a mechanism that may explain how alpha hydroxyl acids (AHAs) -- the key ingredient in cosmetic chemical peels and wrinkle-reducing creams -- work to enhance skin appearance. An understanding of the underlying process may lead to better cosmetic formulations as well as have medical applications.
The findings were published in the Journal of Biological Chemistry in an article entitled "Intracellular proton-mediated activation of TRPV3 channels accounts for exfoliation effect ...
WASHINGTON, DC—A team at Children's National Medical Center has found that external stimulation has an impact on the postnatal development of a specific region of the brain. Published in Nature Neuroscience, the study used sensory deprivation to look at the growth and collection of NG2-expressing oligodendrocyte progenitor cells (NG2 cells) in the sensory cortex of the brain. This type of research is part of the Center for Neuroscience Research focus on understanding the development and treatment of white matter diseases.
NG2 cells can develop into oligodendrocytes progenitor ...
A University of Houston researcher has developed a nanoparticle coating for solar panels that makes it easier to keep the panels clean, maintaining their efficiency for longer and reducing the maintenance and operations costs.
The patent-pending coating developed by physics professor Seamus "Shay" Curran, director of UH's Institute for NanoEnergy, has successfully undergone testing at the Dublin Institute for Technology and will undergo field trials being conducted by an engineering firm in North Carolina.
Curran said the June testing in Ireland and the field trials ...
If a hurricane's path carries it over large areas of fresh water, it will potentially intensify 50 percent faster than those that do not pass over such regions, meaning it has greater potential to become a stronger storm and be more devastating, according to a study co-written by a group of researchers at Texas A&M University.
Ping Chang, professor of oceanography and atmospheric sciences and director of the Texas Center for Climate Studies, along with his former student, Karthik Balaguru, now at the Department of Energy's Pacific Northwest National Laboratory, are the ...
URBANA – A study that examined how rural farmers in Ethiopia learn new farming techniques and adopt them on their own farms discovered that learning from a friend was a stronger motivator than learning from neighbors in close proximity.
The goal of the study was to find out how farmers in Ethiopia learn and ultimately adopt new agricultural technologies such as using fertilizers in the production of grains, trying new grain crop varieties, and installing an irrigation system to grow new high-value fruit and vegetable crops.
"One strategy used by extension in developing ...
ROCHESTER, Minn. -- A sedentary lifestyle is a common cause of obesity (http://www.mayoclinic.com/health/obesity/DS00314), and excessive body weight and fat in turn are considered catalysts for diabetes (http://www.mayoclinic.com/health/diabetes/DS01121), high blood pressure (http://www.mayoclinic.com/health/high-blood-pressure/DS00100), joint damage (http://www.mayoclinic.com/health/arthritis/DS01122/DSECTION=risk-factors) and other serious health problems. But what if lack of exercise itself were treated as a medical condition? Mayo Clinic physiologist Michael Joyner, ...
