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This was corroborated by clinical data, which demonstrated that CRC patients resistant to cetuximab had HER2 amplification or elevated levels of circulating heregulin ( 3.3 Modulation of the MET and KRAS MET activation has been found to confer resistance to cetuximab and panitumumab in CRC ( 3.4 Tumor microenvironment 3.4.1 Tumor-associated fibroblasts and cancer stem cells Hepatocyte growth factor, secreted by TAFs, was found to bind to MET receptors and lead to the activation of MAPK and Akt signaling, conferring resistance to cetuximab in colon cancer stem-like cells ( Through genomic and transcriptomic analysis on CRCs, cetuximab resistance was found to be associated with NF1 and non-canonical RAS/RAF aberrations
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