The EGF Receptor Family as Therapeutic Targets in Breast Cancer

摘要: Many studies have suggested an association between overexpression of receptor tyrosine kinases (RTKs) from the EGF (or ErbB) family and breast cancer. The orphan RTK ErbB2/lIER2fieu is highly overexpressed in up to 30% human cancer cases as a consequence gene amplification. ErbB2/HER2/Neu can be activated by simple overexpression, its signaling thought play important role initiation progression ErbB2-positive cancers. In support this, ErbB2/HER2/Neu-targeted therapy (the Herceptin® antibody) has proven valuable many these cases. Other also correlate (EGFR) expression with poor prognosis cancer, but follow-up suggest that this much less robust than ErbB2, requires more careful analysis. A particular problem EGFR, unlike ErbB2/HER2/Neu, cannot simply remaining growth factor-dependent under conditions. It therefore critical analyze EGFR activity itself, rather expression, order establish causal links identify patients for ErbB-targeted therapies. This distinction satisfyingly explained recent crystallographic ErbB members are reviewed here. These structures provide new insight into how EGFR-targeted therapeutic agents function, approaches development novel mechanism-based inhibitors.