Remodeling of dermal adipose tissue alleviates cutaneous toxicity induced by anti-EGFR therapy

Anti-epidermal growth factor receptor (EGFR) therapy-associated cutaneous toxicity is a syndrome characterized by papulopustular rash, local inflammation, folliculitis, and microbial infection, resulting in a decrease in quality of life and dose interruption. However, no effective clinical intervent...

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Published in:eLife 2022-03, Vol.11
Main Authors: Chen, Leying, You, Qing, Liu, Min, Li, Shuaihu, Wu, Zhaoyu, Hu, Jiajun, Ma, Yurui, Xia, Liangyong, Zhou, Ying, Xu, Nan, Zhang, Shiyi
Format: Article
Language:English
Subjects:
Adipocytes
Adipose tissue
Adipose Tissue - metabolism
Adipose tissues
Animal models
Animals
anti-EGFR therapy
Antitumor activity
Atrophy
Biopsy
Body fat
Cancer
Cancer Biology
Cell Biology
cutaneous toxicity
dermal adipose tissue
Epidermal growth factor
Epidermal growth factor receptors
ErbB Receptors
Exanthema
Folliculitis
Hair
Health aspects
Humans
Infections
Inflammation
Interleukin 6
Interleukin-6 - genetics
Lipolysis
Mice
Peroxisome proliferator-activated receptors
PPAR gamma - metabolism
PPARγ
Quality of Life
Rosiglitazone
Skin
Toxicity
Transcription
Wound healing
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Summary:Anti-epidermal growth factor receptor (EGFR) therapy-associated cutaneous toxicity is a syndrome characterized by papulopustular rash, local inflammation, folliculitis, and microbial infection, resulting in a decrease in quality of life and dose interruption. However, no effective clinical intervention is available for this adverse effect. Here, we report the atrophy of dermal white adipose tissue (dWAT), a highly plastic adipose tissue with various skin-specific functions, correlates with rash occurrence and exacerbation in a murine model of EGFR inhibitor-induced rash. The reduction in dWAT is due to the inhibition of adipogenic differentiation by defects in peroxisome proliferator-activated receptor γ (PPARγ) signaling, and increased lipolysis by the induced expression of the lipolytic cytokine IL6. The activation of PPARγ by rosiglitazone maintains adipogenic differentiation and represses the transcription of IL6, eventually improving skin functions and ameliorating the severity of rash without altering the antitumor effects. Thus, activation of PPARγ represents a promising approach to ameliorate cutaneous toxicity in patients with cancer who receive anti-EGFR therapy.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.72443