Sung, Yejin Hong, Seung Taek Jang, Mihue Kim, Eun Sun Kim, Chansoo Jung, Youngmee Youn, Inchan Kwon, Ick Chan Cho, Seung-Woo Ryu, Ju Hee 2024-01-19T08:02:46Z 2024-01-19T08:02:46Z 2023-12-21 2023-12 0142-9612 https://pubs.kist.re.kr/handle/201004/113030 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 tumorbearing 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. English Pergamon Press Ltd. Predicting response to anti-EGFR antibody, cetuximab, therapy by monitoring receptor internalization and degradation Article 10.1016/j.biomaterials.2023.122382 1 Biomaterials, v.303 Biomaterials 303 Y scie scopus 001113648700001 2-s2.0-85177178021 Engineering, Biomedical Materials Science, Biomaterials Engineering Materials Science Article GROWTH-FACTOR RECEPTOR COLORECTAL-CANCER PATIENTS MONOCLONAL-ANTIBODY PROTEIN-DEGRADATION CATHEPSIN-B INHIBITION CHLOROQUINE ACTIVATION MUTATIONS TUMORS Receptor degradation Predicting response Fluorescence imaging EGFR-targeted therapy Activatable probe