Prediction of response to drug therapy of cancer. A review of in vitro assays.

Cancer chemotherapy has witnessed a great deal of progress since the introduction of the nitrogen mustards in the 1940s. Unfortunately, individual patients with apparently identical tumour histologies do not always respond identically to the same drug regimen. Determining the sensitivity and resistance of an organism before treatment has been the standard of care in infectious diseases for many years, while in oncology treatment has been initiated according to tumour histology rather than the tumour's sensitivity to a given agent. Attempts to individualise therapy have been the goal of oncologists since the 1950s. Since that time a number of in vitro assays have been developed to predict therapeutic outcome prior to the start of therapy. In the 1970s, with the introduction of the human tumour stem cell assay, it was generally believed that oncology was on the threshold of entering an era of predictive in vitro chemosensitivity testing. Unfortunately, this assay was shown to have a number of technical drawbacks including the low plating efficiencies of many primary tumour samples which thus limits the percentage which can be evaluated, leaving us still at this threshold today. Several recent developments, such as the Kern assay, which measures inhibition of radioactive precursors into tumour cells in the presence of antineoplastic agents, ATP bioluminescence assays, and the fluorescent cytoprint assay offer the promise of rapid and sensitive results. Other assays, such as the tetrazolium-based MTT and the sulphorhodamine blue assay appear to hold more promise in the screening and evaluation of potential new agents in established tumour cell lines than for evaluating chemosensitivity of clinical specimens. However, before a particular assay can be considered as an in vitro test of chemosensitivity or resistance, controlled prospective studies must be carried out to validate the assay in a number of different tumour types.