Chemosensitivity testing of human neoplasms using the soft agar colony assay

An in vitro soft agar assay for cloning of primary human tumour cells and sensitivity testing to anticancer agents has been developed by Hamburger and Salmon (human tumour stem cell assay, HTSCA). Based on the stem cell model, this assay may predict chemosensitivity for a defined tumour cell subpopulation of human solid neoplasms. But, methodological problems like the representative quality of a tumour sample, the disaggregation as well as the limited plating efficiency have to be solved before the clinical value of this test can be evaluated. Depending on the histological tumour type a sufficient colony growth for chemosensitivity testing can only be obtained in about 1/3 of all cases. Because of the limited biopsy material, more than five anticancer agents can only be tested in half of all assays. Paradoxical dose-response relationships for cytostatic agents or radiation in vitro point to artifacts. In vivo pharmacokinetics can only be partly imitated by in vitro conditions. Quality-control trials using an established cell line reveal a variability of the in vitro test conditions for certain agents. In addition, the testing of different tumour biopsy samples of the same patient yields variable results. In spite of the methodological problems, large in vivo-in vitro trials show sufficient correlations. The results reflect the high proportion of resistance of human solid tumours. Further development and improvement of the assay promises application of the test system in preclinical testing of anticancer agents.