Resistance to anti-EGFR monoclonal antibodies in the treatment of head and neck carcinoma
DOI:
https://doi.org/10.30827/ars.v62i4.20980Keywords:
cetuximab; head and neck carcinoma; mechanisms of resistance; monoclonal antibodies; nimotuzumab; predictive biomarkers of responseAbstract
Introduction: Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) have shown clinical benefit in advanced stages of head and neck carcinoma; however, despite encouraging initial results, clinical studies show that there are patients who present rates very poor or null response with its use.
Method: A review of the scientific literature was carried out in the specialized sources Medline, Cochrane Library and academic Google on the molecular mechanisms of resistance that may be involved in reducing the efficacy of the monoclonal antibodies cetuximab and nimotuzumab.
Results: In the case of cetuximab, the mechanisms of intrinsic and acquired resistance are exposed, such as: the presence of the EGFR-K521 and AURKA Phe31-Ile polymorphisms, the hot spots activating PIK3CA and KRAS/HRAS mutations, the loss of PTEN protein expression, mutations in the extracellular domain of EGFR, overexpression of MET and induction of epithelial–mesenchymal transition, as well as some mechanisms involving the AKT/PI3K, RAS/RAF/MEK/ERK and JAK/STAT pathways. About nimotuzumab, the literature refers that the best clinical results with its use have been associated with EGFR overexpression.
Conclusions: The greatest challenges in head and neck carcinoma are understanding resistance to these therapies and identifying predictive biomarkers of response for proper patient selection. Although there are multiple proposals for biomarkers that are published, they require their validation in prospective clinical trials for their introduction into routine clinical practice. The need to increase studies on the mechanisms of resistance to nimotuzumab is suggested.
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