Multicellular Resistance: A New Paradigm to Explain Aspects of Acquired Drug Resistance of Solid Tumors
This extract was created in the absence of an abstract.
Excerpt
The study of the cellular and molecular basis of acquired drug resistance in cancer has been dominated by a single experimental approach for the past two decades. This approach consists of exposing established tumor cell lines—usually obtained from solid tumors—to increasing concentrations of a single cytotoxic drug. Conventional two-dimensional monolayer cell culture systems, in which the cells are exposed over prolonged periods of time, are generally used so that drug-resistant mutant subpopulations expressing very high levels of resistance (e.g., 10- to 1000-fold) in a stable or semi-stable fashion are selected. This invariably leads to the isolation of so-called “unicellular” resistant mutants, that is, tumor cells which express their resistance properties at the single-cell level, as a result of biochemical alterations having an underlying genetic basis. The assumption has always been that a similar process takes place in cancer patients exposed to chemotherapy whose tumors may initially respond (i.e., regress, or...
