01:19pm Wednesday 18 October 2017

Using the Structure of the Epidermal Growth Factor Receptor to Fight Cancer

Several cancer drugs, including Herceptin, Erbitux, Iressa and Tarceva fight tumors by blocking EGFR and related receptors, notes Mark A. Lemmon, PhD, Professor and Chair of Biochemistry and Biophysics at the University of Pennsylvania School of Medicine. 

EGFR has a split personality at the cell surface, with two different classes (high-affinity and low-affinity), whose origins have been a mystery since the 1970s. Now, a new paper from the Lemmon lab published recently in Cell explains the difference between these two classes by examining the structure of EGFR and its interactions with EGF. The researchers took advantage of unique properties of the fruit fly equivalent of human EGFR as a window into the molecules’ structures. They found that the EGF receptor acts like a two-stage switch. “Two growth factors can bind to the receptor that signals across the membrane,” explains Lemmon. “With no receptors bound, the receptor is fully off. But, it looks as if there is a different type of signal if just one of the sites is filled as compared to when EGF is bound to both.” Interestingly, the insulin receptor is known to have similar properties.

Check out an explanation of the findings by Lemmon and Diego Alvarado, PhD, formerly a postdoc in the Lemmon lab on Cell’s PaperFlick:

Daryl E. Klein, PhD, most recently a PhD student in the Lemmon lab, was also a co-author on the Cell paper.  The work in the Lemmon lab was funded by the National Cancer Institute.

 

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Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System, which together form a $3.6 billion enterprise. 

Penn’s School of Medicine is currently ranked #2 in U.S. News & World Report’s survey of research-oriented medical schools, and is consistently among the nation’s top recipients of funding from the National Institutes of Health, with $367.2 million awarded in the 2008 fiscal year. 

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Additional patient care facilities and services include Penn Medicine at Rittenhouse, a Philadelphia campus offering inpatient rehabilitation and outpatient care in many specialties; as well as a primary care provider network; a faculty practice plan; home care and hospice services; and several multispecialty outpatient facilities across the Philadelphia region.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2009, Penn Medicine provided $733.5 million to benefit our community.

 

 


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