Context
An increasingly fruitful avenue in cancer therapeutics is the use of agents targeting signal transduction pathways. Trastuzumab (Herceptin), a humanised monoclonal antibody directed against the tyrosine kinase receptor HER2, is one such agent that is proving valuable in the treatment of HER2-overexpressing breast cancer. Unfortunately, responses to trastuzumab vary in magnitude and can also be short lived. These clinical limitations result from acquisition of trastuzumab resistance by the cancer cells. Elucidation of the signal transduction mechanisms underlying resistance would potentially indicate new therapeutic strategies to prevent or delay the resistant state. The present in vitro study investigates whether signalling initiated by the insulin-like growth factor-1 receptor (IGF-1R), an additional tyrosine kinase receptor important in breast neoplasia, enables breast cancer cells to resist trastuzumab inhibition.