In vitro chemosensitivity testing and its clinical application in human gliomas

Abstract

Several in vitro chemosensitivity assays have been developed for predicting clinical response to chemotherapeutic and biologic agents, alone and in combinations. The most widely accepted assay is the colony forming assay (CFA) which assesses the clonogenic capability of stem cells. Other methods include growth inhibition assays by evaluating cell number; thymidine incorporation; or amino acid uptake. More recently an automatic colorimetric technique utilizing crystal violet dye or a tetrazolium (MTT) vital dye has been developed for more rapid assessment of cytotoxic or growth inhibitory activity in vitro. Several reports have compared the results of in vitro tests with patients' clinical response. Two major problems affect the predictive value of in vitro chemosensitivity tests. The foremost is cellular heterogeneity which exists within a single tumor as well as between tumors. Artificial selective pressure inherent to tissue culture system is the other problem. In general, in vitro tests predict clinical resistance more consistently than clinical sensitivity. However, chemosensitivity assays remain useful in screening new agents and preclinical modeling of clinical trials.