OHSU researcher develops first animal model to treat devasting head and neck cancers

PORTLAND, Ore. - An Oregon Health & Science University Cancer Institute research laboratory has developed a novel mouse model designed specifically to study the often devastating head and neck squamous cell cancers. Xiao-Jing Wang, M.D., Ph.D., and colleagues report their research breakthrough in the May 15 issue of Genes & Development.

"This is the first animal model that mimics human head and neck cancer at both the pathological and the molecular levels with 100 percent incidence," Wang said.

While scientists have identified some genes involved in head and neck squamous cell carcinoma (HNSCC), overall, progress has been hampered by the lack of an animal model to study the development and progression of the disease.

"This model will provide a valuable tool to screen for novel therapeutic and preventive approaches for this often deadly cancer," said Wang, head of the Division of Molecular Biology of Head and Neck Cancer in the OHSU School of Medicine and a member of the OHSU Cancer Institute.

Head and neck squamous cell carcinoma is the sixth most common cancer in the United States. It has a low survival rate - fewer than 50 percent of head and neck patients survive beyond five years, and this rate has not changed in the past 20 years, despite progress in developing therapies for other cancers. Patients are usually resistant to routine chemotherapy and radiation therapy. In addition, the quality of life for survivors is usually miserable because the location of the cancer often destroys structures critical to speaking, breathing and swallowing.

In their research, Wang and her colleagues engineered a strain of mice to specifically lack expression of the transforming growth factor beta receptor II (TGFbRII) in epithelial cells of the oral cavity. By then introducing activating mutations in either the H-ras or K-ras (two different isoforms of the Ras GTPase), the researchers were able to induce invasive HNSCC with 100 percent incidence.

"Head and neck lesions developed from this mouse model have many molecular alterations similar to those found in HNSCC patients. Additionally, we have identified several new biomarkers that data suggest may be good targets for HNSCC therapy," Wang said.

Wang was recruited to OHSU to study head and neck cancers. Through her research and through personal acquaintances, her passion was stirred to help people with this type of disfiguring cancer.

"Before I came to OHSU, a woman who was helping me here with my new house asked what was bringing me to Portland. When I told her it was to lead OHSU's research on head and neck cancer, she said, 'Oh, my god, we were meant to meet. My husband was just diagnosed with head and neck cancer.' During my interactions with her after we moved to Portland, I realized how much this disease impacts patients and their family members. Then, only a few months later, a family friend was diagnosed with head and neck cancer. These two cases made me realize that this terrible disease could happen to people all around us, even our loved ones, and inspired me to my best effort in leading this study," Wang said.

"It was a true team effort of the head and neck cancer research division, especially with Dr. Shilong Lu, the first author on this study, who made the major contribution to this model," Wang said. Shilong LU, M.D., Ph.D., is research assistant professor of otolaryngology/head and neck surgery in the OHSU School of Medicine.

Peter Andersen, M.D., F.A.C.S., associate professor of otolaryngology/head and neck surgery in the OHSU School of Medicine; and Christopher L. Corless, M.D., professor of pathology in the OHSU School of Medicine, and member of the OHSU Cancer Institute, are co-authors on this study.

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Particulars: Wang is head of the Division of Molecular Biology of Head and Neck Cancer in the OHSU School of Medicine; a member of the OHSU Cancer Institute; and a research professor of otolaryngology/head and neck surgery, with joint appointments as research professor of cell and developmental biology as well as dermatology in the medical school.

Visit www.OHSU.edu/news to view all OHSU news releases.


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