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Several clinical studies have found that low expression levels of AREG and EREG are related to the low response rate to cetuximab in KRAS-WT CRC patients, but not in CRC patients with KRAS-mutation ( 4.1 Strategies to overcome resistance caused by mutations in EGFR in mCRC A second-generation FDA-approved human EGFR mAb, necitumumab has been shown to bind to EGFR that harbors all reported cetuximab- and panitumumab-resistant mutations except for those at position G441 ( Oligoclonal combination inhibitors that can bind to the mutated ECD of EGFR are new approaches to targeting EGFR that are expected to overcome resistance caused by EGFR ECD mutations

These therapeutic strategies possess high selectivity, especially when activated by GSH localized in the tumor [80]