Research progress on the mechanisms of drug resistance to cetuximab treatment in metastatic colorectal cancer

VernacularTitle:西妥昔单抗治疗转移性结直肠癌耐药机制的研究进展
Author: Xu JIANJIANG ¹ ; Liu TAO ; Wang XU ; Ma MINGLI ; Jiang LEI
Author Information

1. 兰州大学第一临床医学院兰州市730000
Publication Type:Journal Article
Keywords: metastatic colorectal cancer (mCRC); epidermal growth factor receptor (EGFR); cetuximab; drug resistance
From: Chinese Journal of Clinical Oncology 2024;51(21):1120-1124
CountryChina
Language:Chinese
Abstract: Cetuximab is a monoclonal antibody (mAb) targeting the epidermal growth factor receptor (EGFR) for the treatment of metastat-ic colorectal cancer (mCRC). However,most patients treated with cetuximab experience disease progression due to the development of sec-ondary drug resistance,presenting a significant challenge in managing cetuximab therapy. Existing studies have found that cetuximab resist-ance mechanisms are not only linked to the RAS/RAF/PIK3CA genetic mutations but also closely associated with the abnormal activation of PI3K/AKT/mTOR,Wnt/β-catenin,c-MET/HGF,and RAS-MAPK signaling pathways. Additionally,HER2 and MET amplification,microsatellite instability,changes in tumor metabolism,and alterations in the tumor microenvironment may also contribute to cetuximab resistance in pa-tients. This review focuses on the potential molecular mechanisms of cetuximab resistance in the treatment of mCRC,and provides new ideas for overcoming cetuximab resistance in clinic.