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Biomaterials, Volume 303, December 2023, 122382 | https://doi.org/10.1016/j.biomaterials.2023.122382 Predicting response to anti-EGFR antibody, cetuximab, therapy by monitoring receptor internalization and degradation

Yejin Sung^a,b,1, Seung Taek Hong ^a,c,1, Mihue Jang ^a, Eun Sun Kim ^d, Chansoo Kim^e, Youngmee Jung ^a, Inchan Youn ^a, Ick Chan Kwon ^a,f, Seung-Woo Cho ^b,g,h, Ju Hee Ryu^a

^aBiomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea

^bGraduate Program in Bioindustrial Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea

^cDivision of Biohealthcare, Department of Echo-Applied Chemistry, Daejin University, 1007 Hoguk-ro, Pocheon-si, Gyeonggi-do, 11159, Republic of Korea

^dDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, 20841, Republic of Korea

^eAI/R Lab., Computational Science Centre & ASSIST, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul, 02792, Republic of Korea

^fKU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea

^gDepartment of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, 03722, Republic of Korea

^hCenter for Nanomedicine, Institute for Basic Science (IBS), Seoul, 03722, Republic of Korea

¹These authors contributed equally to this work.

Corresponding authors: Seung-Woo Cho, Ju Hee Ryu

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.

논문정보

형식Research article
게재일2023년 12월 (BRIC 등록일 2023-11-20)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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