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Predicting response to anti-EGFR antibody, cetuximab, therapy by monitoring receptor internalization and degradation

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Title
Predicting response to anti-EGFR antibody, cetuximab, therapy by monitoring receptor internalization and degradation
Author(s)
Sung, Yejin; Hong, Seung Taek; Jang, Mihue; Kim, Eun Sun; Kim, Chansoo; Jung, Youngmee; Youn, Inchan; Chan Kwon, Ick; Seung-Woo Cho; Ryu, Ju Hee
Publication Date
2023-12
Journal
Biomaterials, v.303
Publisher
Elsevier Ltd
Abstract
Anti-epidermal growth factor receptor (EGFR) antibody, cetuximab, therapy has significantly improved the clinical outcomes of patients with colorectal cancer, but the response to cetuximab can vary widely among individuals. We thus need strategies for predicting the response to this therapy. However, the current methods are unsatisfactory in their predictive power. Cetuximab can promote the internalization and degradation of EGFR, and its therapeutic efficacy is significantly correlated with the degree of EGFR degradation. Here, we present a new approach to predict the response to anti-EGFR therapy, cetuximab by evaluating the degree of EGFR internalization and degradation of colorectal cancer cells in vitro and in vivo. Our newly developed fluorogenic cetuximab-conjugated probe (Cetux-probe) was confirmed to undergo EGFR binding, internalization, and lysosomal degradation to yield fluorescence activation; it thus shares the action mechanism by which cetuximab exerts its anti-tumor effects. Cetux-probe-activated fluorescence could be used to gauge EGFR degradation and showed a strong linear correlation with the cytotoxicity of cetuximab in colorectal cancer cells and tumor-bearing mice. The predictive ability of Cetux-probe-activated fluorescence was much higher than those of EGFR expression or KRAS mutation status. The Cetux-probes may become useful tools for predicting the response to cetuximab therapy by assessing EGFR degradation. © 2023 The Authors
URI
https://pr.ibs.re.kr/handle/8788114/14620
DOI
10.1016/j.biomaterials.2023.122382
ISSN
0142-9612
Appears in Collections:
Center for Nanomedicine (나노의학 연구단) > 1. Journal Papers (저널논문)
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