Novel Small Molecules Downregulate CDK1 Expression and Inhibit Wnt/β-Catenin Signaling in Cutaneous Squamous Cell Carcinoma by Targeting Its Distinct Tumor-Specific Cellular Landscape

The study investigates the effects of small molecules KY19382 and KY19334 on cutaneous squamous cell carcinoma (cSCC) by targeting the Wnt/β-catenin signaling pathway. These molecules were found to inhibit the malignant phenotype of cSCC cells by suppressing cyclin-dependent kinase 1 (CDK1) expression, which is typically elevated in cSCC patient samples. The study validated the role of CDK1 in cellular transformation and Wnt/β-catenin pathway activation through CDK1 knockdown experiments. Additionally, these molecules reduced carcinogenesis in a mouse skin model. The findings suggest that KY19382 and KY19334 could be potential therapeutic agents for treating cSCC and other cancers associated with CDK1 overexpression, as well as diseases linked to CXXC5 accumulation.