Research progress on the mechanisms of drug resistance to cetuximab treatment in metastatic colorectal cancer
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.
metastatic colorectal cancer (mCRC)epidermal growth factor receptor (EGFR)cetuximabdrug resistance
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