UVB-Induced Premalignant Skin Lesions: Novel Role of Dopamine D2 Receptors Identified
Posted: Friday, May 21, 2021
Preclinical findings presented in Cancer Prevention Research demonstrate that treating ultraviolet B (UVB)-induced cutaneous lesions by stimulating dopamine D2 receptors may significantly reduce the development of malignant squamous cell cancer by suppressing VEGF-induced angiogenesis. Sujit Basu, MD, PhD, of The Ohio State University Comprehensive Cancer Center, and colleagues believe that these relatively inexpensive and safe agents may be worthy of study in clinical trials to prevent and treat these cutaneous lesions, particularly in cases where surgery may cause severe disfiguration.
“Unlike the presently used anti-VEGF agents, dopamine D2 receptor agonists do not cause hypertension, a significant side effect of currently used anti-VEGF agents due to their compensatory effects on the cardiovascular system,” the authors added.
In this trial, the authors exposed mice to UVB irradiation for 16 weeks. After the exposure, the mice were divided into three groups: a control group, a group treated with the dopamine D2 agonist receptor quinpirole (a psychoactive agent often used to manage Parkinson’s disease and restless legs syndrome), and a cohort pretreated with the receptor antagonist eticlopride (investigational agent) followed by quinpirole.
The authors found that the number of cutaneous tumors and the tumor burden significantly decreased in UVB-irradiated mice after treatment with quinpirole compared with those in the control group. Pretreatment with eticlopride seemed to counteract the effects of quinpirole, confirming the results were through dopamine D2 receptors. In addition, they found that quinpirole did not appear to impact VEGF expression and that the antagonist “significantly” inhibited epidermal proliferation in UVB-irradiated animals compared with those in the vehicle-treated control group. Of note, no grade 3 papilloma or cutaneous squamous cell carcinomas were seen in mice treated with quinpirole.
Disclosure: The authors reported no conflicts of interest.