Sensitivity and resistance to EGF-R inhibitors: approaches to enhance the efficacy of EGF-R antibodies.

The epidermal growth factor receptor (EGF-R) constitutes one of the most broadly targeted antigens in tumor therapy since it is commonly expressed on many epithelial cancers, as well as on glioblastomas. Both EGF-R-directed tyrosine kinase inhibitors and monoclonal antibodies have been approved, but clinical response rates are often limited. A more detailed understanding of the mechanisms underlying sensitivity or resistance against EGF-R inhibitors may assist in identifying patient populations who optimally benefit from currently available reagents. In addition, these insights may guide the development of more effective molecules. In this short review, we will summarize some of the current knowledge in this rapidly evolving field with particular emphasis on EGF-R-directed antibodies.