CDNA Technologies and their application to drug resistance research: power, potential and problems

The effectiveness of systemic chemotherapy is dramatically limited by both intrinsic and acquired drug resistance. Several new technologies have been developed over the last decade to more rapidly identify underlying genetic alterations that impart a drug-resistant phenotype. Techniques such as cDNA -based subtraction technologies, SAGE analysis, and most recently cDNA arra y and high-density micro-array technologies have rapidly expanded our abili ty to detect changes in RNA transcription in drug-resistant tumors. These t echnologies are currently being applied to generate a large number of new h ypotheses regarding the regulatory molecules underlying the drug-resistance phenotype. These techniques suggest that there is a large number of transc riptional changes which occur in the drug-resistance phenotype and future w ork will need to focus on dissecting which of these transcriptional changes are central to the drug resistance phenotype, both in vitro, and more impo rtantly within clinical neoplasia. (C) 2000 Harcourt Publishers Ltd.