Drug resistance mechanisms in cancer cells: a proteomics perspective.

Chemotherapy forms a significant component of the treatment of many human cancers. The failure of tumor cells to respond to the action of cytotoxic drugs is referred to as drug resistance. Mechanisms mediating resistance are multifaceted and often not clearly defined. The challenge of elucidating the link between drug response and resistance, and then integrating the information for the purpose of therapeutic intervention, is a major task that awaits scientists in the post-genomic era. Rapid advances in proteome technologies have made it possible to simultaneously identify multiple proteins involved in drug refractory cancers. This methodology has the potential to isolate novel proteins, including those associated with resistance to specific drugs and those involved in conferring broad resistance to a range of compounds. The identification of key proteins will lead to the possibility of developing molecular, biological or pharmaceutical strategies to modify the action of such proteins when their inappropriate structure or expression is contributing to drug-resistant disease.