A team led by a scientist from the Florida campus of The Scripps Research Institute (TSRI) has identified a new biomarker linked to better outcomes of patients with head and neck cancers and non-small cell lung cancer.
The work could help scientists develop new diagnostics and therapies and help physicians determine the best long-term treatments for patients with these cancers.
Dr. Laura Niedernhofer studies DNA damage, cell function and cancer biomarkers at the Florida campus of the Scripps Research Institute. Her work could lead to better diagnostics and more personalized therapies.
Credit: Scripps Research Institute
The findings, which were published this week online ahead of print by the journal Cancer, focus on a protein called Choline phosphate cytidylyltransferase-α CCT-α or CCTα, an "antigen" that prompts the immune system to produce antibodies against it.
"Based on what we found, a high CCTα expression appears to be indicative of survival, making CCTα a promising biomarker," said Laura Niedernhofer, a TSRI associate professor who led the study with Gerold Bepler of the Karmanos Cancer Institute. "Our findings suggest that CCTα may, in fact, be more important in determining outcomes in patients with both types of cancer than the already established ERCC1."
The new study, in fact, turns previous studies on ERCC1 on their heads. Dozens of large clinical trials are being conducted using expression of the ERCC1 DNA-repair protein as a determinant of whether patients with lung, pancreatic, gastric, colorectal, esophageal or ovarian cancer should be treated with platinum-based therapy, a very potent but toxic DNA-damaging agent.
However, the new research suggests that these positive results were not actually due to ERCC1, but to CCTα—which also binds to the antibody most frequently used to measure ERCC1 expression. "Our results show CCTα may be a better predictor of patient outcomes than expression of ERCC1," said Niedernhofer.
While ERCC1 is associated with DNA repair, CCTα is involved in the synthesis of a major component of cell membranes, active in membrane-mediated signaling and embryo survival.
The new results were based on an examination of samples from 187 patients with non-small cell lung cancer and 60 patients with head and neck squamous cell carcinomas.
CCTα expression was associated with longer survival rates, including for patients with non-small cell lung cancer who were treated with surgery alone—without the use of platinum-based chemotherapy drugs and associated toxic side effects.
The first author of the study, "Choline Phosphate Cytidylyltransferase-α is a Novel Antigen Detected by the Anti-ERCC1 Antibody 8F1 with Biomarker Value in Patients with Lung and Head and Neck Squamous Cell Carcinomas," is Alec Vaezi of the University of Pittsburgh.
In addition to Niedernhofer, Bepler and Vaezi, other authors include Agnes Malysa and Wei Chen of the Karmanos Cancer Institute; and Nikhil Bhagwat, Jennifer Rubatt, Brian Hood, Thomas Conrads, Lin Wang and Carolyn Kemp of the University of Pittsburgh. For more information, see http://onlinelibrary.wiley.com/doi/10.1002/cncr.28643/abstract
The study was supported by National Institute of Environmental Health Sciences (grant R01-ES016114), the National Cancer Institute (grants R01-CA129343 and P50-CA097190) and the American Head and Neck Society.
About The Scripps Research Institute:
The Scripps Research Institute (TSRI) is one of the world's largest independent, not-for-profit organizations focusing on research in the biomedical sciences. TSRI is internationally recognized for its contributions to science and health, including its role in laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. An institution that evolved from the Scripps Metabolic Clinic founded by philanthropist Ellen Browning Scripps in 1924, the institute now employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute's graduate program, which awards PhD degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see http://www.scripps.edu.
Eric Sauter | EurekAlert!
A human respiratory tissue model to assess the toxicity of inhaled chemicals and pollutants
26.03.2015 | R&D at British American Tobacco
Sci-Fly study explores how lifeforms know to be the right size
26.03.2015 | Cincinnati Children's Hospital Medical Center
In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...
The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.
As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...
When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.
The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe.
Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...
Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.
From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...
25.03.2015 | Event News
19.03.2015 | Event News
17.03.2015 | Event News
26.03.2015 | Trade Fair News
26.03.2015 | Trade Fair News
26.03.2015 | Life Sciences