The Riddle of Cetuximab-Related Skin Toxicity: (1)H-NMR Sebum Analysis Revealed Dynamic Lipid Alterations Associated with Skin Toxicity Development in Metastatic Colorectal Cancer Patients

SIMPLE SUMMARY: The etiology of the skin toxicity that is a common side effect of cetuximab is still under debate. In this study, proton nuclear magnetic resonance ((1)H-NMR) analysis of the sebum of 30 metastatic colorectal cancer patients, collected at different time points during cetuximab administration, was performed. Both sebum production and composition were found to be affected by cetuximab treatment. These specific sebum lipid alterations could help to better understand the development of cetuximab-induced skin toxicity and could be useful for improving skin lesion prevention and treatments. ABSTRACT: The epidermal growth factor receptor inhibitor (EGFRIs) treatments are commonly associated with the development of adverse skin effects. This study aims to investigate the lipid composition change in sebum during cetuximab-based treatment in an attempt to identify specific metabolic signatures useful in predicting the occurrence of severe skin toxicity. Sebum from 30 metastatic colorectal cancer (mCRC) patients was collected at three time points during the targeted therapy by the application of Sebutape(®) on the forehead, and the major lipid classes were analyzed and quantified by (1)H-NMR. Univariate analysis was performed to reveal significant alterations among patients in sebum production as well as lipid composition and over the course of cetuximab therapy. A transient but significant decrease in sebum production associated with a reduction in the relative content of triglycerides (TG) and squalene (SQ) was found to be induced by cetuximab administration. The reduction of these two lipid classes was also found to be associated with the severity of skin rash experienced by patients. The results of this study indicate that cetuximab-based treatment can reduce sebum gland activity, leading to an overall decrease in sebum production and the induction of specific modifications to its composition. The extent of the loss of skin barrier function may be important for determining the severity of skin toxicity development.