Understanding and managing locally advanced basal cell carcinoma: insights into pathogenesis, therapeutic strategies, and the role of hedgehog pathway inhibitors

Understanding and managing locally advanced basal cell carcinoma (BCC) is crucial given its substantial prevalence and potential for local tissue destruction. While BCC typically exhibits low metastatic potential, its high incidence underscores the need for enhanced therapeutic strategies. Locally advanced BCC presents unique challenges, often necessitating aggressive interventions to prevent disfigurement and functional impairment. The emergence of hedgehog pathway inhibitors (HHIs) offers promising therapeutic avenues by targeting aberrant hedgehog signaling, a key driver in BCC pathogenesis. Thus, elucidating the pathogenesis of locally advanced BCC and exploring the role of HHIs are critical endeavors in effectively managing this prevalent carcinoma. Epidemiologically, BCC primarily affects individuals with fair skin and chronic sun exposure, with an increasing incidence noted among younger age groups. Risk factors include UV radiation exposure, familial history of skin cancer, immunosuppression, and genetic syndromes such as basal cell nevus syndrome and xeroderma pigmentosum. Pathogenetically, BCC arises from cells in the skin's epidermis, with hedgehog pathway activation being a primary genetic driver, involving mutations in PTCH1 and SMO. Resistance to hedgehog inhibitors may occur due to genetic changes, complicating treatment strategies. BCC is characterized by low immunogenicity, which hinders immune response and contributes to treatment challenges. Enhanced understanding of the epidemiology, risk factors, and pathogenesis of locally advanced BCC, along with the development of targeted therapeutic approaches such as hedgehog pathway inhibitors, is essential for effectively managing this prevalent carcinoma and improving patient outcomes.