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University of Pittsburgh Schools of the Health Sciences 

Pitt Team Gets Federal Grant to Find New Head and Neck Cancer Drugs

PITTSBURGH, Aug. 19, 2010 – Researchers at the University of Pittsburgh Cancer Institute (UPCI) and the University of Pittsburgh School of Medicine have been awarded an $800,000 federal grant to develop agents to inhibit a cellular signaling protein that plays a key role in triggering and supporting the growth of many cancers, including cancers of the head and neck.

A member of a protein class called Signal Transducers and Activators of Transcription, activated STAT3 in excess levels can drive the transformation of healthy cells into cancer, said principal investigator Jennifer R. Grandis, M.D., professor of otolaryngology and pharmacology at Pitt, and director of the Head and Neck Program at UPCI. The abnormality has been found in not only head and neck cancers, but also in many malignancies including breast, prostate and lung cancer.

“This protein can send signals to other molecules encouraging the replication and spread of cancer cells, promoting new blood vessel growth to tumors and suppressing the immune response against the disease,” Dr. Grandis explained. “Animal studies have shown that inhibiting it can shrink tumors and prolong survival, so it represents an important target for therapies against a range of cancer types.”

With funding from the National Cancer Institute, part of the National Institutes of Health, Dr. Grandis and her team will identify and develop small-molecule inhibitors of STAT3 activation, which is present in squamous cell carcinoma of the head and neck (SCCHN) and in 95 percent of all head and neck cancers. The best candidates will be tested in animal models of SCCHN.

Current treatments for SCCHN include surgery and chemoradiation, and the only approved molecular approach is the monoclonal antibody cetuximab, which inhibits epidermal growth factor receptor (EGFR).

“Although EGFR expression is common in these tumors, cetuximab works only in a subset of patients, leaving the rest likely to succumb to their cancers,” Dr. Grandis noted. “It’s possible that STAT3 activation is contributing to resistance to the drug, so blocking it could make cetuximab treatment more effective.”

Co-principal investigators include John Lazo, Ph.D., Allegheny Foundation Professor, and Paul A. Johnston, Ph.D., research associate professor, both in the Department of Pharmacology and Chemical Biology, Pitt School of Medicine.

About UPCI

As the only NCI-designated comprehensive cancer center in western Pennsylvania, UPCI is a recognized leader in providing innovative cancer prevention, detection, diagnosis, and treatment; bio-medical research; compassionate patient care and support; and community-based outreach services. UPCI investigators are world-renowned for their work in clinical and basic cancer research.

About the University of Pittsburgh School of Medicine

As one of the nation’s leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1997 and now ranks fifth in the nation, according to preliminary data for fiscal year 2008. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region’s economy. For more information about the School of Medicine, see www.medschool.pitt.edu.

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