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Helping skin cells differentiate could be key to treating common skin cancer

August 20, 2019

PHILADELPHIA - The outer layer of the skin completely replaces itself every two to four weeks, but when this process is blocked, cancer can grow. A new study from researchers in the Perelman School of Medicine at the University of Pennsylvania has now identified a key regulator of that block known as LSD1, as well as a way to genetically influence the skin to grow in a way that prevents this block from happening. This is the first study to show that LSD1 - a regulator involved in telling parent cells what type of specific cells their lineage should become as they reproduce - plays a role in the growth of non-melanoma skin cancers, and that blocking LSD1 could be an effective, targeted treatment method for those cancers, which are the most common in the world. The journal Cell Reports published the findings today.

Cutaneous squamous cell carcinoma (cSCC) is a skin cancer caused by the abnormal growth of skin cells. Together with a similar type of cancer known as basal cell carcinoma (BCC), they outnumber all other human cancers combined. While many patients can have these cancers removed, others are not candidates for surgery and need alternative treatment options, which can include chemotherapy. Previous research has shown that these types of cancers thrive when skin cells, which are constantly renewing, don't differentiate themselves as they reproduce.

"Our study shows that targeting LSD1 can force the skin cells down a differentiation path, which could open the door to new topical therapies that can ultimately turn tumor cells into healthier, more normal cells," said the study's senior author Brian C. Capell, MD, PhD, an assistant professor of Dermatology and a member of Penn's Epigenetics Institute and Abramson Cancer Center. The co-lead authors on the study are Shaun Egolf, a graduate student, and Yann Aubert, PhD, a postdoctoral fellow, both in Capell's lab.

LSD1 is typically elevated in many types of cancer, and there are several inhibitors that attempt to target it. But until now, no one has shown its role in repressing the genes the skin needs for healthy turnover. That knowledge could open the door to a new treatment method that blocks LSD1 with a skin cream or other topical therapy.

"By knocking out LSD1, we can essentially turn the switch back on that would tell the skin to differentiate in a healthy way," Capell said.

Researchers say work is already underway to prove the concept can work, which would pave the way for human clinical trials.
-end-
This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08AR070289, 1P30AR069589-01), the Damon Runyon Cancer Foundation, the Dermatology Foundation, and a Developmental Research Award from the Penn-Wistar SPORE in Skin Cancer funded by the National Cancer Institute (NCI P50CA174523).

Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $7.8 billion enterprise.

The Perelman School of Medicine has been ranked among the top medical schools in the United States for more than 20 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $425 million awarded in the 2018 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center--which are recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report--Chester County Hospital; Lancaster General Health; Penn Medicine Princeton Health; and Pennsylvania Hospital, the nation's first hospital, founded in 1751. Additional facilities and enterprises include Good Shepherd Penn Partners, Penn Home Care and Hospice Services, Lancaster Behavioral Health Hospital, and Princeton House Behavioral Health, among others.

Penn Medicine is powered by a talented and dedicated workforce of more than 40,000 people. The organization also has alliances with top community health systems across both Southeastern Pennsylvania and Southern New Jersey, creating more options for patients no matter where they live.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2018, Penn Medicine provided more than $525 million to benefit our community.

University of Pennsylvania School of Medicine

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