The ErbB receptors as targets for breast cancer therapy.

Breast carcinomas express high levels of ErbB receptors and their ligands, and their overexpression has been associated with a more aggressive clinical behavior. For these reasons therapies directed at these receptors have the potential to be useful anti-cancer treatments. A series of monoclonal antibodies (MAbs)3 directed against the EGF (ErbB1) receptor and the closely related HER2/Neu (ErbB2) 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 one of these antibodies, trastuzumab, a humanized anti-ErbB2 MAb, has been documented in patients with breast cancer in a series of clinical trials and has recently been approved for the therapy of patients with metastatic ErbB2 overexpressing breast cancer. In addition to antibodies, compounds that inhibit receptor tyrosine kinases have shown significant preclinical activity and are currently being evaluated in the clinic.