In vitro sensitivity assays in cancer: a review, analysis, and prognosis

Tumors are complex systems consisting of heterogeneous cancer cells as well as normal cells with each exhibiting unique drug sensitivity spectra. There have been many attempts to design in vitro systems to determine drug response to tumors. The most widely used system is the clonogenic assay. which has demonstrated some clinical predictivity. However, the clonogenic assay has been shown to have negative aspects, including low frequency of evaluation, clump artifacts, lack of cytotoxic end-points and disruption of normal cell-cell interactions existing in a true tissue environment. Newer models are described utilizing cytotoxic as well as cell-proliferation end-points, and maintenance of three-dimensional tissue architecture in vitro. It is concluded that less artifactual, more realistic models can be used to select more tumor-specific drugs which themselves in turn will make in vitro chemosensitivity assays more useful for cancer patients.