Therapeutic Advances in Advanced Basal Cell Carcinoma

Simple Summary Basal cell carcinoma (BCC) is the most common form of skin cancer. In advanced stage, BCC exhibits aggressive behavior, leading to local tissue destruction. Thus, a multidisciplinary approach and specialized treatment strategies are required for effective disease management and improvement of the patient quality of life. For low-risk disease, surgical intervention is the modality of choice while radiotherapy is indicated in unresectable tumor, positive margins post-surgery when re-excision is not feasible, and in the presence of high-risk features for recurrence. For locally advanced and metastatic disease, the emergence of systemic treatments including hedgehog inhibitors and immune checkpoint inhibitors has significantly improved the outcomes. Nonetheless, developing resistance to therapy presents a significant challenge in management. Consequently, development of novel therapeutic strategies is ongoing to address improving treatment efficacy.Abstract Basal cell carcinoma (BCC) is the most common type of cancer with an estimated 3.6 million cases diagnosed annually in the US alone. While most cases are treatable with low recurrence rates, 1-10% progress to an advanced stage which can behave aggressively, leading to local destruction and posing substantial challenges in management. The pathogenesis often involves dysregulation of the patched/hedgehog protein family, a pivotal pathway targeted by recently approved therapies. Furthermore, the role of immunotherapy is evolving in this type of tumor as we learn more about tumor microenvironment dynamics. In recent years, there have been advancements in the therapeutic landscape of advanced BCC, offering patients new hope and options for managing this complex and potentially life-threatening condition. In this review, we aim to provide a comprehensive overview of this disease, including the risk factors, underlying pathogenesis, current treatment options of advanced disease, and the ongoing exploration and development of novel therapies.