Establishment of in-vitro models of chemotherapy resistance.

Chemotherapy resistance is one of the most prevalent obstacles to the treatment of cancer, resulting in increased mortality and prolonged exposure to cytotoxic agents with no treatment benefit. One of the tools utilized in the study of mechanisms of chemotherapy resistance are established cell lines derived from human neoplasms. These cell lines can be challenged in vitro with controlled chemotherapy doses to produce chemotherapy-resistant variants. Analysis of these novel chemotherapy-resistant cell lines may then identify genetic and proteomic changes which are associated with the resistant phenotype. Two very important mediators of chemotherapy resistance (P-glycoprotein and multidrug resistance protein-1) were initially identified in chemotherapy-resistant cell lines. To make these in-vitro studies clinically relevant it is, however, necessary to duplicate as far as possible the treatment conditions used in vivo. Considerations should include clinically relevant drug concentrations, such as those derived from peak plasma values, and the type of treatment schedule to be employed.