Topical Treatment Quickly Clears Precancerous Skin Lesions
A combination of two FDA-approved drugs – a topical chemotherapy and an immune-system-activating compound – was able to rapidly clear actinic keratosis lesions from patients participating in a clinical trial. Standard treatment for this common skin condition, which can lead to the development of squamous cell carcinoma, takes up to a month and can elicit several unpleasant side effects. The report from Massachusetts General Hospital (MGH) investigators was published online in December 2016 and will appear in the January 2017 issue of the Journal of Clinical Investigation.
A release from the hospital quotes senior author Shadmehr Demehri, MD, PhD, of the MGH Center for Cancer Immunology and the Cutaneous Biology Research Center as saying, “The high tumor clearance rate, short treatment duration and favorable side-effect profile highlight the remarkable effectiveness of this approach, compared with currently available treatments. But more importantly, the unprecedented ability of this combination therapy to directly activate the adaptive immune system against skin cancer precursors holds great promise to establish an immune memory within treated skin capable of preventing future cancer development.”
Caused by long-term exposure to sunlight, actinic keratosis is characterized by rough, scaly patches on the skin. Very common in older individuals with fair complexions, actinic keratosis is the third most common reason for consulting a dermatologist in the U.S. If untreated, actinic keratosis lesions can progress to squamous cell carcinoma, the second most common form of skin cancer. Current topical treatments for actinic keratosis cause side effects – such as pain, crusting and susceptibility to infection – and need to be applied for up to four weeks.
Calcipotriol, an FDA-approved treatment for psoriasis, induces expression in the skin of an immune system activator called TSLP. While overexpression of TSLP is associated with the allergic inflammation seen in asthma and eczema, it has been noted that individuals with these allergic conditions appear to be less susceptible to skin cancer. Other studies have supported the ability of TSLP to suppress skin cancer development, which led Demehri’s team to investigate its potential against actinic keratosis.
Experiments with a mouse model of skin cancer development showed that twice-weekly application of calcipotriol both induced TSLP expression and delayed tumor development. When tumors did develop, they were fewer and smaller than in mice not treated with calcipotriol. An experiment in which calcipotriol was applied to the ears of mice while skin cancer was induced to develop on the backs of the animals resulted in elevated blood levels of TSLP and the suppression of tumor development, implying that brief TSLP-inducing treatment could lead to a lasting systemic antitumor immune response.