Skin cancer, encompassing subtypes like melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC), is a major public health concern due to its prevalence as the most common cancer in the United States, affecting one in five Americans. Despite advances like immune checkpoint inhibitors and BRAF inhibitors, many patients remain unresponsive, with cancers such as advanced melanoma and Merkel cell carcinoma showing resistance. This highlights the complexity of its pathogenesis involving genetic mutations, immune responses, and environmental factors like UV exposure.

The adoption of systems genetics in skin cancer research offers a hopeful avenue by delving into the intricate genetic and environmental interactions that drive the disease. This approach merges genetics, genomics, and systems biology to map out the connections between genetic variants, molecular targets, and pathways influencing disease susceptibility and progression. Insights gained, such as the link between Ptch1 gene mutations and BCC, Tp53, and Notch1 with SCC, and the BRAFV600E mutation in melanoma, are crucial for developing more effective and personalized treatments by pinpointing new diagnostic and therapeutic targets.

Reference: Kim MJ, Kulkarni V, Goode MA, et al. Utilizing systems genetics to enhance understanding into molecular targets of skin cancer. Exp Dermatol. 2024;33(3):e15043. doi: 10.1111/exd.15043.