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Pathways to Discovery: Spring 2012

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Lab Findings Lead to Clinical Trial for Head and Neck Cancer

The cancer cell-killing effect of this combination is very evident.
—H. Rosie Xing, PhD

A UChicago researcher is investigating a question that has long puzzled cancer specialists: Why does head and neck cancer (HNC) have such a low response rate to a commonly used treatment?

H. Rosie Xing, PhD, assistant professor of pathology, has found a molecular connection that may lead to more effective treatments for HNC, which is the sixth most common cancer worldwide.

Once the disease metastasizes, treatment options are limited and patient survival drops to an average of 10 months.

The Study
The epidermal growth factor receptor (EGFR) exists on cell surfaces and plays a role in regulating cell growth. Dr. Xing said she became curious when she learned that EGFR is overexpressed in 90% of HNC patients.

Dr. Xing collaborated with a computational biologist and his research team to look at genomic information from clinical samples. Unlike other cancers, such as breast and lung cancer, little has been studied about HNC on a genomic level. In addition to EGFR, the researchers studied mTor, a protein that also regulates cell growth.

Dr. Xing discovered that when the mTor pathway is blocked, cancer cells adapt by using EGFR, but when both the mTor and EGFR pathways are simultaneously blocked, the tumor regresses. "The cancer cell-killing effect of this
combination is very evident," she said.

Dr. Xing and colleagues also looked at changes that occur when the tumor cells interact with the surrounding environment, known as the tumor stroma.

Mark Lingen, DDS, PhD, associate professor of pathology and scientific director of the Human Tissue Resource Center, compared cells from precancerous patients with cells from patients with HNC to determine differences in the stroma.

"We found there's one component that is uniquely present in the cancer state that is absent in the premalignant state––myofibroblasts," said Dr. Xing. Myofibroblasts
produce collagen and can change the structure of a tumor.

Previous studies have shown that aggressive breast and pancreatic cancers are rich in myofibroblasts, which may induce angiogenesis, the formation of new blood vessels to fuel cell growth.

Using a treatment that combined an EGFR inhibitor with an mTor inhibitor, the researchers saw that the EGFR inhibitor was effective at killing cancer cells, while the mTor inhibitor was effective at depleting myofibroblasts and inhibiting angiogenesis.

The Next Steps
Dr. Xing shared her research findings with Walter Stadler, MD, Fred C. Buffett Professor of Medicine and Surgery, and Tanguy Seiwert, MD, assistant professor of medicine, who helped launch a randomized, Phase II multicenter clinical trial to test this therapeutic combination.

"I think this is a prime example of translation where a bench result may have direct impact on the clinical side," said Dr. Seiwert. "We really need a better treatment and this seems like an avenue to try to develop one."

UChicago is leading the trial, which is open at multiple academic centers across the nation through the UCCCC's Phase II Clinical Trials Network and the Mayo Clinic
Cancer Research Consortium. Dr. Seiwert said he expects to have results in approximately 1 year.

Rosie Xing