Clinical Correlations of Drug Sensitivity in the Human Tumor Stem Cell Assay

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Abstract
We have applied an in vitro soft-agar tumor-colony assay (which is now applicable to a variety of human cancers) to measurement of in vitro sensitivity to drugs and prediction of clinical response to cancer chemotherapy. The assay predicts drug resistance with 96% accuracy and sensitivity (in heavily pretreated patients) with 62% accuracy. On a pharmacokinetic basis the zone in vitro sensitivity for any given drug was only 5%–10% of the clinical concentration-time product (Cxt) achievable. This suggests that intratumoral drug concentrations in vivo may be lower than those in the plasma, and/or that > 2 log kills of tumor stem cells (not measurable in the assay) are required for clinical response. Serial in vitro studies showed that acquisition of drug resistance is a common clinical phenomenon which can be directly detected and quantitated in vitro.