11:23pm Monday 20 November 2017

Cross Talk Between Oncogenes Suggests Treatment Combination in Esophageal Cancer, According to Penn Study

Using a three-dimensional (3-D) tissue culture system that mimics esophageal tissue growth, Anil K. Rustgi, MD, chief of Gastroenterology at the University of Pennsylvania School of Medicine, and colleagues have discovered molecular cross talk between the oncogene Met, which is overexpressed in the majority of these tumors; the epidermal growth factor receptor (EGFR) oncogene; and the tumor suppressor gene p53. The results highlight a targeted therapy that may hold promise for treating ESCC.

Using the 3-D culture system, the team identified a sequence of events that may lead to tumor formation and progression in this type of esophageal cancer. They hypothesized that a mutation in the p53 gene and overexpression of EGFR lead to tumor initiation and the start of tumor invasion by triggering expression of the Met protein. Once tumor cells invade the surrounding tissue, signals secreted by neighboring non-cancerous cells further activate the Met receptor, which in turn stimulates more growth and invasion. Consistent with this model, Rustgi and colleagues find that inhibitors of Met activity in their 3-D system prevent this pattern of tumor invasion.

Those data, which the team presented on Sunday afternoon, April 18th at the American Association of Cancer Research meeting, suggest that treating patients with an EGFR inhibitor and a Met inhibitor may be more effective than treating them with just one inhibitor at a time. Also, the newly uncovered interaction between these key cancer-promoting genes may occur in other cancers and may suggest ways to improve targeted therapy combinations, Rustgi says. He discussed the development and use of the 3-D model system in a session on Saturday, April 17th.

“There has been a notion of an interrelationship between Met and EGFR oncogenes, and this work reveals also a potential link between Met and the p53 mutation,” Rustgi says. Specifically, Rustgi’s team found that genetic changes or drugs that inhibit the Met receptor in epithelial cells or its binding partner, hepatocyte growth factor (HGF), block ESCC invasion. Additionally, Met activation increases when a cell overexpresses EGFR and has a mutated copy of p53, both of which are common genetic mutations in ESCC. “These results highlight the potential benefit of the therapeutic targeting of HGF/Met signaling in esophageal squamous cell cancer and potentially other squamous cancers where this pathway is deregulated.”

 

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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. 

Penn Medicine’s patient care facilities include:

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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