Cigarette smoke is the dominant cause of lung cancer in the United States, accounting for an estimated 90 percent of all cases. While only 10-20 percent of smokers develop lung cancer in their lifetime, there are currently no tools available to identify which of the approximately 90 million current and former smokers in the U.S. are at the highest risk.
Unfortunately, diagnosis is most often made at a very advanced stage where treatment is largely ineffective. The damage caused by cigarette smoke, however, is not limited solely to the lung, but rather constitutes a 'field of injury' throughout the entire respiratory tract that is exposed to the toxin. Consistent with this idea, study lead author Avrum Spira, MD, MSc, chief of the section of computational biomedicine in the department of medicine at BUSM and his colleagues, previously developed a gene expression-based biomarker measured in the cytologically normal bronchial airway epithelium that reflects an individual's physiologic response to smoking and distinguishes smokers with and without lung cancer. Although this biomarker is successful at diagnosing lung cancer, it does not identify the signaling pathways underlying these gene expression changes.
Using a novel gene-expression based approach to define oncogenic pathway signatures, the researchers, in collaboration with Dr. Andrea Bild at the University of Utah, have now discovered that the expression of genes belonging to one specific cancer-related pathway, PI3K, are activated in the cells that line the airway of smokers with lung cancer. This gene expression activity in the normal cells of the proximal airway precedes the development of lung cancer and may be reversed with a specific chemopreventive agent (myo-inositol) that targets this pathway.
"This finding is significant as these cells can be obtained in a relatively non-invasive fashion from the airway of smokers at risk for lung cancer, and does not require invasive sampling of lung tissue where lung tumors normally arise," said Spira, who is also an associate professor medicine and pathology at BUSM.
The BUSM researchers then went on to validate their findings by measuring the biochemical activity of this pathway in the airway epithelial cells from an independent group of smokers with and without lung cancer. "We found that this PI3K pathway gene expression activity is decreased in the airway of high-risk smokers who had regression (or improvement) of their premalignant lesions following treatment with a potential lung cancer chemopreventive agent known as myo-inositol, and demonstrated that myo-inositol inhibits the PI3K pathway in lung cancer cell lines," he added.
According to the researchers, the data suggests that measuring this airway gene expression activity can help determine which specific cancer pathways have been deregulated within an individual smoker, allowing one to tailor a specific drug that will target the pathway to reduce that individual's risk of lung cancer. "This represents a critical advance in the field of lung cancer prevention as there are currently no effective strategies for lung cancer prevention among high risk smokers. Our work has the potential to help address the enormous and growing public health burden associated with lung cancer, the leading cause of cancer-related death among men and women in the US and the world," added Spira.
Funding for this study was provided by the National Institutes of Health.
Spira is one of the founders of Allegro Diagnostics Inc., a molecular diagnostics company that plans to market the gene expression biomarker.
Gina DiGravio | EurekAlert!
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy