(Press-News.org) Chapel Hill, NC – In a paper published today in the journal Cell, a team from the University of North Carolina at Chapel Hill unveils the first broad-based test for activation of protein kinases "en masse", enabling measurement of the mechanism behind drug-resistant cancer and rational prediction of successful combination therapies.
Kinases are proteins expressed in human tissues that play a key role in cell growth, particularly in cancer. Of the 518 known human kinases, about 400 are expressed in cancers, but which ones and how many are actually active in tumors has been difficult to measure. Tremendous efforts have been made to develop kinase inhibitors as cancer treatments, which have resulted in key drugs such as Herceptin®, Tykerb®, and Gleevec®. However, in spite of the effectiveness of this class of cancer drugs, most cancers eventually become resistant. The UNC team has developed a test that can measure both the presence and activity of 60-70 percent of all kinases simultaneously, allowing investigators to see how cancers evade treatment with kinase inhibitors so that they can combine drugs to block resistance.
Gary Johnson, PhD, the project's principal investigator, says, "Single-agent kinase inhibitors are promising in principle, but often fail in practice because the network of tumor kinases learns how to get around the inhibitor, leading to rapid drug resistance. We're very excited about the test our lab has developed because it works very well in a model of breast cancer to predict the success of combination therapies."
Johnson, who is the Kenan Distinguished Professor and chair of the department of pharmacology in the UNC School of Medicine and a member of UNC Lineberger Comprehensive Cancer Center, is working with UNC Breast Center medical director Lisa Carey, MD, UNC Lineberger director Shelley Earp, MD, and surgical oncologist Keith Amos, MD, to perform clinical trials using the technology with the goal of real-time, personalized therapies for breast cancer.
"One of the most frustrating things as an oncologist is when a patient's tumor develops resistance to a treatment," says Carey, who is also a member of UNC Lineberger. "We are excited about the ability to examine tumor samples before, during, and after kinase inhibitor treatment to see how the tumor kinase profile changes, and potentially respond to those changes using different inhibitors."
The team hopes to be able to track and define the kinase 'reprogramming' that takes place in tumors during therapy and to use the new test to identify combinations of drugs that will block the cancer's adaptive behavior that leads to drug resistance. A patent application has been filed for the testing technology.
###James Duncan, PhD; PhD student Marty Whittle; and Kazuhiro Nakamura, MD/PhD lead the research effort in Johnson's lab. Other members of the research team include Amy Abell, PhD; PhD student Alicia Midland; Jon Zawistowski, PhD; Nancy Johnson, MS; Deborah Granger, BS; and PhD student Nicole Vincent Jordan from the Johnson lab. Also contributing to the research project were David Smalley, PhD, Shawn Gomez, PhD; and Lee Graves, PhD; from the Department of Pharmacology, Jian Jin, PhD; and Xin Chen, PhD; of the Eshelman School of Pharmacy, Steven Frye, PhD of the Eshelman School of Pharmacy and UNC Lineberger; Pei-Fen Kuan, PhD; David Darr, Xiaping He, PhD; Bing Zhou, PhD; Jerry Usuary, PhD; Ben Major, PhD; Katherine Hoadley, PhD; Charles Perou, PhD; Norman Sharpless, MD; and William Kim, MD; all members of UNC Lineberger.
The research was funded by the National Institute for General Medical Sciences and accelerated by two ARRA grants. It was initially funded with an innovation award from the UNC Lineberger University Cancer Research Fund and has also been supported by developmental funds from UNC's NCI-sponsored Specialized Program of Research Excellence (SPORE) in Breast Cancer and the Breast Cancer Research Foundation.
Kinase test may yield big gains for drug-resistant cancers
2012-04-13
ELSE PRESS RELEASES FROM THIS DATE:
High levels of phthalates can lead to greater risk for type-2 diabetes
2012-04-13
There is a connection between phthalates found in cosmetics and plastics and the risk of developing diabetes among seniors. Even at a modest increase in circulating phthalate levels, the risk of diabetes is doubled. This conclusion is drawn by researchers at Uppsala University in a study published in the journal Diabetes Care.
"Although our results need to be confirmed in more studies, they do support the hypothesis that certain environmental chemicals can contribute to the development of diabetes," says Monica Lind, associate professor of environmental medicine at the ...
Drastic changes needed to curb most potent greenhouse gas
2012-04-13
Meat consumption in the developed world needs to be cut by 50 per cent per person by 2050 if we are to meet the most aggressive strategy, set out by the Intergovernmental Panel on Climate Change (IPCC), to reduce one of the most important greenhouse gases, nitrous oxide (N2O).
This is the finding from a new study, published today, 13 April, in IOP Publishing's Environmental Research Letters, which also claims that N2O emissions from the industrial and agricultural sectors will also need to be cut by 50 per cent if targets are to be met.
The findings have been made ...
Breakthrough discovery unveils 'master switches' in colon cancer
2012-04-13
A team of researchers at Case Western Reserve University School of Medicine have identified a new mechanism by which colon cancer develops. By focusing on segments of DNA located between genes, or so-called "junk DNA," the team has discovered a set of master switches, i.e., gene enhancer elements, that turn "on and off" key genes whose altered expression is defining for colon cancers. They have coined the term Variant Enhancer Loci or "VELs," to describe these master switches.
Importantly, VELs are not mutations in the actual DNA sequence, but rather are changes in proteins ...
Researchers call for a new direction in oil spill research
2012-04-13
Inadequate knowledge about the effects of deepwater oil well blowouts such as the Deepwater Horizon event of 2010 threatens scientists' ability to help manage and assess comparable events in future, according to an article that a multi-author group of specialists will publish in the May issue of BioScience. Even federal "rapid response" grants awarded to study the Deepwater Horizon event were far more focused on near-surface effects than on the deepwater processes that the BioScience authors judge to be most in need of more research.
The article, by a team led by Charles ...
Pride and prejudice: Pride impacts racism and homophobia
2012-04-13
A new University of British Columbia study finds that the way individuals experience the universal emotion of pride directly impacts how racist and homophobic their attitudes toward other people are.
The study, published in the April issue of Personality and Social Psychology Bulletin, offers new inroads in the fight against harmful prejudices such as racism and homophobia, and sheds important new light on human psychology.
"These studies show that how we feel about ourselves directly influences how we feel about people who are different from us," says Claire Ashton-James, ...
Determining a stem cell's fate
2012-04-13
PASADENA, Calif.—What happens to a stem cell at the molecular level that causes it to become one type of cell rather than another? At what point is it committed to that cell fate, and how does it become committed? The answers to these questions have been largely unknown. But now, in studies that mark a major step forward in our understanding of stem cells' fates, a team of researchers from the California Institute of Technology (Caltech) has traced the stepwise developmental process that ensures certain stem cells will become T cells—cells of the immune system that help ...
New research puts focus on earthquake, tsunami hazard for southern California
2012-04-13
San Francisco, April 12, 2012 -- Scientists will convene in San Diego to present the latest seismological research at the annual conference of the Seismological Society of America (SSA), April 17-19.
This year's meeting is expected to draw a record number of registrants, with more than 630 scientists in attendance, and will feature 292 oral presentations and 239 poster presentations.
"For over 100 years the Annual Meeting of SSA has been the forum of excellence for presenting and discussing exciting new developments in seismology research and operations in the U.S. ...
Traffic harms Asturian amphibians
2012-04-13
The roads are the main cause of fragmenting the habitats of many species, especially amphibians, as they cause them to be run over and a loss of genetic diversity. Furthermore, traffic harms two abundant species that represent the amphibious Asturian fauna and have been declared vulnerable in Spain: the midwife toad (Alytes obstetricans) and the palmate newt (Lissotriton helveticus).
"But midwife toad and palmate newt populations have very different sensitivities to the effects of roads" Claudia García-González, researcher at the University of Oviedo, told SINC. "These ...
Nutrient and toxin all at once: How plants absorb the perfect quantity of minerals
2012-04-13
In order to survive, plants should take up neither too many nor too few minerals from the soil. New insights into how they operate this critical balance have now been published by biologists at the Ruhr-Universität in a series of three papers in the journal The Plant Cell. The researchers discovered novel functions of the metal-binding molecule nicotianamine. "The results are important for sustainable agriculture and also for people – to prevent health problems caused by deficiencies of vital nutrients in our diet" says Prof. Dr. Ute Krämer of the RUB Department of Plant ...
Herschel sees dusty disc of crushed comets
2012-04-13
Astronomers using ESA's Herschel Space Observatory have studied a ring of dust around the nearby star Fomalhaut and have deduced that it is created by the collision of thousands of comets every day.
Fomalhaut, a star twice as massive as our Sun and around 25 light years away, has been of keen interest to astronomers for many years. With an age of only a few hundred million years it is a fairly young star, and in the 1980s was shown to be surrounded by relatively large amounts of dust by the IRAS infrared satellite. Now Herschel, with its unprecedented resolution, has ...