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Experimental drug shows promise against head and neck cancer

29.04.2009
HDAC inhibitor effective against tumor cell lines

A laboratory study by researchers at Albert Einstein College of Medicine of Yeshiva University suggests that an anti-cancer compound studied for treating blood cancers may also help in treating cancers of the head and neck. The work is reported in the April 28th online edition of the Journal of Pathology.

Head and neck cancer refers to tumors in the mouth, throat, or larynx (voice box). Each year about 40,000 men and women develop head and neck cancer in the U.S., making it the country's sixth-most common type. Surgery, chemotherapy and/or radiation are the main treatment options but can cause serious side effects. Better treatments are needed, since only about half of patients with head and neck cancer survive for five or more years after diagnosis.

The Einstein study involved a new class of chemotherapy agents known as histone deacetylase (HDAC) inhibitors, which affect the availability of genes that are transcribed and translated into proteins. In many types of cancer, out-of-control cell growth results from certain genes that are either too active or not active enough in producing proteins. HDAC inhibitors appear to combat cancer by restoring the normal expression of key regulatory genes that control cell growth and survival.

The Einstein researchers focused on a particular HDAC inhibitor known as LBH589 that has already shown some success in clinical trials involving people with cancers of the blood. The researchers found that LBH589 succeeded in killing tumor cells that had been removed from head and neck cancer patients and grown in the laboratory.

"This report shows that an HDAC inhibitor is effective on head and neck cancer cell lines, and that is the first step toward use in humans," said Richard Smith, M.D., the lead clinician involved in the study. Dr. Smith is associate professor of clinical otorhinolaryngology-head & neck surgery and associate professor of surgery at Einstein and is also vice-chair of otorhinolaryngology-head & neck surgery at Einstein and Montefiore.

The researchers also identified a set of genes whose expression levels change in response to the HDAC inhibitors—a finding that may help doctors identify patients most likely to respond to the drug. Plans call for testing LBH589 on head and neck tumor cells from more patients so that the set of genes that respond to the drug can be more firmly established.

"We are performing studies in mice to confirm these laboratory results, which hopefully will progress to human clinical trials of LBH589 for the treatment of head and neck cancer," said Michael Prystowsky, M.D., Ph.D., chair and professor of pathology at Einstein and corresponding author of the article.

Other Einstein researchers involved in the study were Alfred Adomako, Nicole Kawachi, Wendy McKimpson, Quan Chen, Nicolas Schlecht, Geoffrey Childs and Thomas Belbin. The title of the paper is "The histone deacetylase inhibitor LBH589 inhibits expression of mitotic genes causing G2/M arrest and cell death in head and neck squamous cell carcinoma cell lines."

About Albert Einstein College of Medicine of Yeshiva University

Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. It is the home to some 2,000 faculty members, 750 M.D. students, 350 Ph.D. students (including 125 in combined M.D./Ph.D. programs) and 380 postdoctoral investigators. Last year, Einstein received more than $130 million in support from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Through its extensive affiliation network involving five hospital centers in the Bronx, Manhattan and Long Island – which includes Montefiore Medical Center, The University Hospital and Academic Medical Center for Einstein – the College runs one of the largest post-graduate medical training program in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training.

Deirdre Branley | EurekAlert!
Further information:
http://www.aecom.yu.edu

Further reports about: Einstein HDAC LBH589 Medical Wellness blood cancer cell growth neck cancer tumor cells

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