Type I Receptor Tyrosine Kinases as Targets for Therapy in Breast Cancer

Breast carcinomas express high levels of type I tyrosine kinase receptors and their ligands. For these reason therapies directed at these receptors have the potential to be useful anti-cancer agents. A series of monoclonal antibodies (MAbs)(3) directed against the EGF receptor and the closely related erbB2/HER2/neu receptor are currently under evaluation. These MAbs have shown promising preclinical activity and "chimeric" and "humanized" MAbs have been produced in order to obviate the problem of host immune reactions. These antibodies are currently being tested in clinical trials either alone or in combination with chemotherapeutic agents. Clinical activity with anti-HER2/neu MAbs has been documented in patients with advanced breast cancer. In addition, compounds that inhibit receptor tyrosine kinases have shown significant preclinical activity and are potential candidates for clinical testing.