Cancer researchers have pursued laboratory techniques to match patients to available drugs since the introduction of cytotoxic chemotherapy. Up until the 1990s, most of the work reflected the prevailing view of cancer as a disease of disregulated cell proliferation (out of control cell growth). Apoptosis and programmed cell death, now fundamental to our modern understanding of human tumor biology, was not known until well after the heyday of in vitro chemosensitivity testing.
By incorporating our new knowledge, we can now re-examine laboratory assays of drug response in the context of drug-induced programmed cell death. While there is interest in the use of genomic analyses for the prediction of chemotherapy response, the painful recognition that genotype does not equal phenotype will continue to limit broad application of these platforms.
Biological pathways rarely follow predicted routes. Efforts to force human biology to behave according to pre-conceived scientific dictates have proven costly and unsuccessful. Whole cell experimental models with the capacity to evaluate all the operative mechanisms of cellular response to injury, provide valid tools for the study of human cancer. Educated by cellular behavior, we can examine molecular processes of interest.