Fox Chase Researcher Receives Grant From NIH to Explore Role of Immune Gene in Breast Cancer

“Every assay that we looked at, when we switched the possum element with the mouse element, and examined T cells for differentiation or function, we saw no change,” Kappes said. “The element that arose 165 million years ago, and had 165 million years to diverge in function, has not diverged at all."
Dietmar J. Kappes, PhD. His research is particularly relevant to HER2-positive breast cancer, a cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2) that promotes the growth of cancer cells. About one in five breast cancers is HER2-positive.

PHILADELPHIA — (August 28, 2019) Dietmar J. Kappes, PhD, has received a five-year, $626,072 grant from The National Institutes of Health to investigate the role of the immune gene ThPOK in breast cancer. Kappes is a professor of blood cell development and cancer at Fox Chase Cancer Center, where he is also director of the Transgenic Mouse Facility.

His research is particularly relevant to HER2-positive breast cancer, a cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2) that promotes the growth of cancer cells. About one in five breast cancers is HER2-positive.

These cancers tend to be more aggressive than other types of breast cancer. They also are less likely to respond to hormone therapy, although treatments that specifically target HER2 are highly effective. Nonetheless, most patients with HER2-positive breast cancer eventually become resistant even to targeted treatments.

Preliminary research has linked poor clinical outcomes for patients with HER2-positive breast cancer to mislocalization of the transcription factor ThPOK. Kappes and his colleagues have used a novel mouse model to establish a causal relationship between ThPOK mislocalization and the development of highly penetrant HER2-positive breast cancer.

Given the central role of HER2 signaling in HER2-positive breast cancer biology, the researchers hypothesize that ThPOK-mediated regulation of these factors enhances HER2-mediated signaling. They also believe that this mechanism represents an important driver of breast cancer development and/or progression that has previously been overlooked.

Besides HER2-positive breast cancer, POK transcription factors also have been implicated in many other cancers. The researchers now implicate mislocalization of ThPOK in breast cancer in both humans and mice. Through this grant, Kappes aims to further elucidate the role of ThPOK in breast cancer by combining novel animal models and molecular approaches.

“These studies have the capacity to shift the basic understanding of how POK factors promote cancer and may lead to new treatments targeting HER2-positive breast cancer and other cancers in which ThPOK is implicated.”

Fox Chase Cancer Center (Fox Chase), which includes the Institute for Cancer Research and the American Oncologic Hospital and is a part of Temple Health, is one of the leading comprehensive cancer centers in the United States. Founded in 1904 in Philadelphia as one of the nation’s first cancer hospitals, Fox Chase was also among the first institutions to be designated a National Cancer Institute Comprehensive Cancer Center in 1974. Fox Chase is also one of just 10 members of the Alliance of Dedicated Cancer Centers. Fox Chase researchers have won the highest awards in their fields, including two Nobel Prizes. Fox Chase physicians are also routinely recognized in national rankings, and the Center’s nursing program has received the Magnet recognition for excellence five consecutive times. Today, Fox Chase conducts a broad array of nationally competitive basic, translational, and clinical research, with special programs in cancer prevention, detection, survivorship, and community outreach. It is the policy of Fox Chase Cancer Center that there shall be no exclusion from, or participation in, and no one denied the benefits of, the delivery of quality medical care on the basis of race, ethnicity, religion, sexual orientation, gender, gender identity/expression, disability, age, ancestry, color, national origin, physical ability, level of education, or source of payment.

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