Aberrant Activation of the Hedgehog Pathway in Cutaneous Melanoma: Therapeutic Potential of Pharmacological Inhibitors

Cutaneous melanoma, a highly aggressive skin cancer, often relapses and metastasizes, necessitating new therapeutic approaches due to resistance to current treatments. This study highlights the aberrant reactivation of the Hedgehog (Hh) pathway in melanoma, identifying it as a promising therapeutic target. Researchers found chronic up-modulation of the Hh pathway in patient-derived cell lines, with reduced expression of PTCH1 and SUFU repressors and increased GLI2, alongside autocrine activation through SHH release. Clinically approved Hh antagonists reduced melanoma cell proliferation and migration, and modulated inflammatory mediators, suggesting their potential repurposing as therapeutic agents for melanoma.