Topical LSD1 inhibitor shows promise for cSSC Tx
- John Evans
- 2 days ago
- 2 min read
Findings from a preclinical study show a topical cream that blocks the immune-suppressing enzyme LSD1 suppressed tumour growth in two models of cutaneous squamous cell carcinoma (cSCC).
The study, published in the Journal of Clinical Investigation, describes how the cream, developed by researchers at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, prevents LSD1 from suppressing immune‑activating pathways in the skin.
“What’s striking is that a simple topical cream can use the skin’s own machinery to recruit and activate immune cells that attack tumours,” said senior author Brian C. Capell, MD, PhD, in a press release from the university. “We are carrying out some more studies to refine the formulation this coming year, and we hope to begin a phase 1 clinical trial in the next one to two years. Ideally, this cream could be used directly on cancerous and precancerous spots.”
Dr. Capell is an assistant professor of Dermatology at the University of Pennsylvania.
The authors note that current options for widespread cSCC lesions, such as chemotherapy, are not selectively targeted to the cancer, and other targeted treatments can be painful. Surgery remains effective but is invasive and carries risks such as infection and scarring. A topical approach that activates anti-tumour immune responses locally could reduce the need for repeated procedures and help prevent progression to invasive cancer, they say.
In the study, researchers formulated a low‑dose topical inhibitor of LSD1, an enzyme that normally acts as a “brake” on certain immune‑activating pathways in epidermal cells. By “lifting the brake,” the cream prompted skin cells to signal for immune help. Those cells played a key role in slowing tumour growth.
Investigators found that blocking retinoic acid signalling, a naturally occurring and important type of basic cellular signalling that tells cells how to grow and develop, reversed many of the skin-level changes induced by the cream. In addition, destroying CD4⁺ T cells (a type of immune cell) eliminated their tumour suppression. The findings suggest the therapy works by priming communication between skin cells and the immune system to enable targeted anti-tumour responses.
While treating skin cancer would be a huge benefit from this treatment, preventing cancer from forming in the first place could have an even larger impact. An estimated 58 million Americans live with skin precancers or early squamous cell carcinomas each year, and a topical treatment could reduce the need for repeated surgeries and lower the number of lesions that progress to invasive cancer. The researchers are also exploring whether taking LSD1 inhibitors orally or by injection could enhance the efficacy of immune checkpoint cancer therapies. These types of therapies are currently effective in only a subset of patients with advanced cSCC.
This research was supported by the U.S. National Institutes of Health (K08AR070289, P30-AR069589, R01AR077615, R01CA262055, R01HL162715, T32GM007170, T32AR007465), the Damon Runyon Cancer Research Foundation, the Dermatology Foundation, and the Skin Cancer Foundation.