Protein identified as cause of skin damage after radiotherapy

Radiotherapy is one of the main treatment forms for cancer. Among its most common side effects is skin damage, right up to chronic inflammations and fibroses. At present, such long-term damage can only be treated symptomatically and leads to thickened, painful, or sensitive skin for months to years after the radiation treatment. A team led by LMU physician Professor Peter Nelson (LMU University Hospital) and Roger Sandhoff and Peter E. Huber from the German Cancer Research Center (DKFZ) has identified a protein called Dickkopf 3 (DKK3) as a main cause of long-term skin damage after radiotherapy – a decisive step for the development of novel, more targeted therapy options.

By investigating mouse models and human cells and tissue samples, the researchers demonstrated that DKK3 is activated after radiotherapy in a certain group of skin cells that are responsible for skin renewal. This activity triggers a chain reaction which promotes inflammations and the formation of scar-like tissue and leads to chronic skin damage. The key findings were driven by the work of LMU students, Li Li and Khuram Shehzad. Their efforts were essential in identifying DKK3 as the critical molecular mediator and in establishing the mechanistic framework presented in the paper. “We also observed similar processes in the kidney,” says Nelson. “This indicates that the activation of DKK3 is a fundamental mechanism that promotes fibrosis in various tissues.”

According to the researchers, these findings underscore that DKK3 represents a promising new treatment target. “Drugs that block DKK3 could one day help prevent or reduce long-term skin damage after radiotherapy and thus improve the quality of life of cancer patients and survivors,” says Nelson. The researchers are currently investigating, moreover, whether this approach could also contribute to the prevention of scar formation in other organs.

L. Li et al.: Wnt-associated DKK3 in keratinocytes mediates radiation induced hyperplasia, dermatitis and skin fibrosis. Signal Transduction and Targeted Therapy, 2026