Mechanism of resistance to cetuximab therapy in colorectal cancer

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Mechanism of resistance to cetuximab therapy in colorectal cancer

The response rate to cetuximab, a chimeric (mouse-human) monoclonal antibody directed against epidermal growth factor receptor (EGFR), in colorectal cancer is low (10–15%), with significant inter-individual variability. Mechanisms proposed thus far to explain resistance to this therapy—such as the emergence of EGFR and KRAS mutations and aberrant ERBB2 signaling—do not account for the total int...

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Mutational analysis of primary and metastatic colorectal cancer samples underlying the resistance to cetuximab-based therapy

PURPOSE Although several molecular markers predicting resistance to cetuximab- or panitumumab-based therapy of metastatic colorectal cancer were described, mutations in RAS proto-oncogenes remain the only predictors being used in daily clinical practice. However, 35%-45% of wild-type RAS patients still do not respond to this anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibody-...

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Cetuximab sensitivity associated with oxaliplatin resistance in colorectal cancer.

BACKGROUND Clinical studies have suggested that the epidermal growth factor receptor (EGFR)-inhibiting antibody cetuximab may have better effect in the third-line treatment of metastatic colorectal cancer, after failure of standard chemotherapy including oxaliplatin, compared to using it up-front in the first line. The reason behind this suggestion is unclear. MATERIALS AND METHODS The effect...

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AXL mediates resistance to cetuximab therapy.

The EGFR antibody cetuximab is used to treat numerous cancers, but intrinsic and acquired resistance to this agent is a common clinical outcome. In this study, we show that overexpression of the oncogenic receptor tyrosine kinase AXL is sufficient to mediate acquired resistance to cetuximab in models of non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), where ...

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Cetuximab in the management of colorectal cancer

Cetuximab, a chimeric IgG1 monoclonal antibody that targets the ligand-binding domain of the epidermal growth factor receptor (EGFR), is active in metastatic colorectal cancer (mCRC). As an IgG1 antibody, cetuximab may exert its antitumor efficacy through both EGFR antagonism and antibody-dependent cell-mediated cytotoxicity. Clinical trials established the role of cetuximab, particularly with ...

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ژورنال

عنوان ژورنال: mAbs

سال: 2012

ISSN: 1942-0862,1942-0870

DOI: 10.4161/mabs.21311