EGF receptor targeting in therapy-resistant human tumors.

The development of resistance against cytotoxic or endocrine therapy limits the number of chemotherapeutic compounds used in the clinic. The receptor for EGF (EGFR) is not only involved in survival signaling, cell migration, metastasis formation and angiogenesis, but also confers reduced responses of tumor cells towards cytotoxic compounds or radiation. Clinical trials designed to combine EGFR inhibitors with standard chemo- or radiation therapy have been successful. Elucidation of some of the molecular mechanisms of EGFR-mediated chemoresistance may lead to novel treatment approaches against molecules linked to EGFR signal transduction. In human breast carcinomas, the presence of EGFR correlates with lack of response towards anti-estrogen therapy suggesting the concomitant inhibition of both the receptors for estrogen and EGF to improve breast cancer therapy.