 As dimerization is important in signal transduction, therapies that target more than one member of the HER family may have greater anti-tumor effect. Recently, data with trastuzumab plus IMC-C224 in human ovarian cancer cells showed greater growth inhibition compared to either monoclonal antibody alone. GW572016 is an orally active dual HER1HER2 kinase inhibitor that blocks signal transduction pathways. This dual inhibition is an attractive therapeutic strategy for epithelial cancers, as ligand-induced HER1HER2 dimerization triggers off potent proliferative and survival signals. In vitro studies with GW572016 have shown marked activity, leading to growth arrest and apoptosis in HER1 and HER2 overexpressing cell lines. GW572016 markedly reduced tyrosine phosphorylation of HER1 and HER2, and activation of MAP kinase and Akt, the downstream effectors of proliferation and survival, respectively. In vitro studies in HER-2 overexpressing cell lines have demonstrated synergistic activity when GW572016 is combined with taxanes. Phase I studies with GW572016 and taxanes have been completed, with results demonstrating that this small molecule inhibitor may be safely combined with chemotherapy with no unanticipated side effects. 