Magdalena Kloc, Laura Jonderko, Katarzyna Herbetko, Karolina Kublińska, Aleksandra Wojno, Oliwia Cichy, Agata Wojno, Anna Karwowska, Sara Suwała, Anna Choromańska
Skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma, remain a major therapeutic challenge due to their prevalence, invasive potential, and the limited efficacy of conventional treatments. Fungal-derived secondary metabolites have emerged as promising sources of anticancer agents, acting through pro-apoptotic, anti-angiogenic, immunomodulatory, and anti-metastatic mechanisms. This review summarizes current evidence on representative fungal compounds - including cordycepin, ganoderic acid D, and immunomodulatory polysaccharides such as lentinan - with particular focus on their activity against skin cancer cells in vitro, in vivo, and in early clinical trials. We further discuss key translational challenges, including production, bioavailability, and toxicity, and highlight the potential of fungal metabolites in combination with chemotherapy, radiotherapy, and immunotherapy. Collectively, the available data indicate that fungal-derived compounds represent promising, though still largely preclinical, candidates for the treatment of skin cancer, warranting further mechanistic and clinical investigation.