Mechanismen van resistentie tegen EGFR/HER2-antilichamen

Monoclonal antibodies against the epidermal growth factor receptors EGFR and HER2 constitute an important advance in the treatment of breast cancer, metastatic colorectal cancer and head and neck tumours. However, resistance against these drugs may occur. The molecular mechanisms of resistance can be attributed to several processes. Extracellular, mutated receptors in the bloodstream may compete with transmembrane receptors. At receptor level ECFR and HER2 can be influenced by, among others, tyrosine kinase receptors such as the insulin-like growth factor 1R. At the intracellular level there can be specific mutations or other mechanisms resulting in a continuous activation of the downstream cascade. Specific biomarkers exist to predict the effect of a therapy with monoclonal antibodies, although these are not conclusive. New markers are (urgently) needed in the future. New therapies to circumvent resistance are being investigated at present.