The Role of Glucose-6-Phosphate Dehydrogenase in Skin Cancer Metabolism: A Paradigm Shift in Treatment Approaches

Skin cancer is one of the most prevalent malignancies in the world, with increasing incidence. In 2022, the World Health Organization estimated over 1.5 million new diagnoses of skin malignancies, primarily affecting the older population. Surgical excision, particularly in the head and neck area, can cause aesthetic deficits and significantly impair patients' quality of life. There are limited therapeutic options for advanced skin malignancies, and the development of resistance to targeted therapy further restricts treatment choices. Cancer metabolism may offer a novel approach to overcome these challenges. The pentose phosphate pathway, along with its rate-limiting enzyme, glucose-6-phosphate dehydrogenase, is essential for both the antioxidative response and the synthesis of ribonucleotides and may play a critical role in the proliferation and growth of cancer cells. This review examines current knowledge on the correlation between altered glucose-6-phosphate dehydrogenase expression and activity and skin cancer progression, with the aim of identifying a potential therapeutic target for treating advanced skin cancer.