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

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 1H-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.

Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022

“…in a plasma analysis of 140 human samples that could differentiate five cancers (liver, lung, gastric, colorectal, and thyroid). 176 It is therefore of no surprise with its known lipid dysregulation and urgency that oncology was the biggest application area in 2022, where the following cancers were studied: bladder, 177 brain, 155 breast, 178 , 179 , 180 , 181 , 182 colorectal, 183 , 184 , 185 , 186 , 187 , 188 endometrial, 189 gallbladder, 190 gastric, 191 kidney, 192 liver, 193 , 194 , 195 , 196 , 197 lungs, 156 , 198 , 199 , 200 nasopharyngeal, 201 ovarian, 202 paediatric, 203 prostate, 204 , 205 and skin. 206 …”

“…Bibliometric analyses of clinical lipidomics publications in 2022 using Scopus search terms “lipidomics” AND “clinic*” on 15 th December 2022 …”

“…Bibliometric analyses of clinical lipidomics publications in 2022 according to separation techniques, detectors, and RPLC columns used …”

“… Bibliometric analyses of clinical lipidomics publications in 2022 according to separation techniques, detectors, and RPLC columns used. 51 , 60 , 61 , 68 , 77 , 155 , 156 , 157 , 166 , 177 , 178 , 179 , 180 , 181 , 182 , 183 , 184 , 185 , 186 , 187 , 188 , 189 , 190 , 191 , 192 , 193 , 194 , 195 , 196 , 197 , 198 , 199 , 200 , 201 , 202 , 203 , 204 , 205 , 206 , 212 , 213 , 214 , 215 , 232 , 233 , 234 , …”

“…[170][171][172][173] Lipidomic analyses have revealed cancer-specific lipid dysregulations that could potentially serve as promising biomarkers for screening purposes, 174,175 as demonstrated by Lee et al in a plasma analysis of 140 human samples that could differentiate five cancers (liver, lung, gastric, colorectal, and thyroid). 176 It is therefore of no surprise with its known lipid dysregulation and urgency that oncology was the biggest application area in 2022, where the following cancers were studied: bladder, 177 brain, 155 breast, [178][179][180][181][182] colorectal, [183][184][185][186][187][188] endometrial, 189 gallbladder, 190 gastric, 191 kidney, 192 liver, [193][194][195][196][197] lungs, 156,[198][199][200] nasopharyngeal, 201 ovarian, 202 paediatric, 203 prostate, 204,205 and skin. 206 To maximize the survival rates of cancer patients, it is important to identify cancer at its early stages, where tumours can be surgically removed or treated with milder drug regimens.…”