Drugs that target the epidermal growth factor receptor, or EGFR, have been used for a number of cancers. But these drugs called EGFR inhibitors, such as cetuximab, have not been very effective against colon cancer.
The new study, however, shows that drugs that target the closely related receptor ERBB3 would probably be much more effective than EGFR inhibitors at treating most colorectal cancers, said David Threadgill, Ph.D., adjunct professor in the department of genetics at UNC and lead author of the study. He also is a member of the UNC Lineberger Comprehensive Cancer Center and a professor in the genetics department at North Carolina State University.
The study is published online August 17 in the Journal of Clinical Investigation.
The researchers genetically blocked ERBB3 in a mouse model of colon cancer and in human colon cancer cell lines. “If you genetically remove ERBB3, as you would if you were pharmacologically targeting it, then the mice rarely develop colon cancer,” Threadgill said.
In the human colon cancer cell lines that are resistant to EGFR inhibitors, cell death increased dramatically when ERBB3 was genetically removed. “So ERBB3 is essential for preventing colon cancer cells from dying,” Threadgill said. Now Threadgill is testing a pharmacologic inhibitor to get the same anti-ERBB3 effect they achieved with genetics. “If we can use an inhibitor to block ERBB3, then it should be a very potent anti-cancer therapeutic,” he said.
More broadly, the study suggests a new path for developing anti-cancer drugs.
Many cancer therapeutics, such as EGFR inhibitors, target proteins that are kinases—enzymes that initiate a cascade of signals that tell cells to reproduce. But ERBB3 is a pseudo-kinase; it functions only by binding with other proteins that have kinase activity.
“This study shows that targets that historically hadn’t been considered because they don’t have the typical activities of a kinase can be equally if not more important in supporting cancer cells,” Threadgill said.
Other UNC co-authors are Ming Yu, a former graduate student in the department of genetics and the Program in Oral Biology; Christina Pannicia, former undergraduate student in biology; and Daekee Lee, formerly of the genetics department and now of Ewha Womans University in Seoul, Republic of Korea. Other co-authors are Eunjung Lee, Hyunok Kim and Kyoungmi Kim of Ewha Womans University; and Jonathan M. Kurie and Yanan Yang of the University of Texas M.D. Anderson Cancer Center.
The study was funded by the National Cancer Institute, the National Science Foundation, and the Korea Science and Engineering Foundation.
Les Lang | EurekAlert!
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences