Chemo-signal therapy, an emerging new approach to modify drug resistance in breast cancer

Recent advances in understanding how response or resistance to cytotoxic drugs develops at the cellular level resulted in the development of novel, non-cytotoxic agents that modulate response the chemotherapy. 'Chemo-signal therapy', the combination of chemotherapy with cellular response modifiers, is a very promising new treatment modality that has entered the arena of clinical trials. Clinical experience with the anti-HER-2 antibody, trastuzumab, in breast cancer has demonstrated that manipulation of growth factor signalling can enhance sensitivity to cytotoxic drugs in a clinically meaningful way. Several other agents that were designed to modulate response to chemotherapy are currently in early phases of clinical drug development. It is likely that some of these new molecules will have a major impact on how chemotherapy will be given in the next decade. This paper will review current clinical research with a select group of chemotherapy response modifiers. We will focus on agents that modulate signal transduction, oncogene expression and apoptosis with an emphasis on breast cancer.