An estimated one in every five Americans will reportedly develop skin cancer at some point during their lives, making the condition an extremely common and problematic disorder across the United States. Fortunately, of the more than 3.5 million nonmelanoma skin cancers that are diagnosed in the U.S. every year, most are highly curable; in fact, even melanoma, a potentially deadly form of skin cancer that can spread to the lymph nodes and internal organs, is treatable if it is detected early. However, dermatology and skin cancer specialists often report unexpected difficulty when it comes to one of the most popular forms of the disease, called basal cell carcinoma. Now, researchers may have uncovered genetic evidence that could explain why and even lead to new treatments.
Basal cell carcinoma, like most skin cancers, is described as a highly treatable form of the disease. Despite this fact, however, dermatologists often report that treatment for skin cancer in advanced cases, which uses a drug called vismodegib, is often only temporarily effective. Moreover, many patients later develop new tumors within a few months, which are resistant to vismodegib.
In an article published in the journal Cancer Cell, a research team from Stanford’s School of Medicine reports that they have traced the origins of the vismodegib resistance, a development which they believe has revealed new skin cancer treatment methods. According to the article, about half of patients with basal cell carcinoma will respond to the drug, which is part of a class of drug compounds called Smoothened inhibitors. However, 20% of these patients will quickly develop resistance to vismodegib. The researchers found that basal cell carcinomas are unusually dependent on the inappropriate activation of the Hedgehog pathway, a cellular signalling cascade. Two classes of mutations in the Smoothened gene, which is found in the Hedgehog pathway, reportedly inhibit vismodegib’s effectiveness by keeping the Smoothened protein active.
In light of this finding, the research team has stated that treatment for skin cancer tumors that are vismodegib-resistant may be made more effective by blocking signalling along the Hedgehog pathway, specifically the Smoothened inhibitors, called Gli antagonists. The researchers say that this could lead to better combination therapies even before treatment begins. However, new treatment for skin cancer may not be the only benefit of this research: the Hedgehog pathway has also been found to be abnormally active in pancreatic, colon, lung, breast and other types of cancers, including a type of brain cancer called medulloblastoma.