Transcription profiling of gene expression in drug discovery and development: the NCI experience.

Eur J Cancer

Developmental Therapeutics Program, National Cancer Institute, Information Technology Branch, Bethesda, MD 20892-7444, USA.

Published: November 2004

Transcript profiling, using microarray or other analogous technologies, to query on a large-scale the expression of genes in tumours or their derivative cell lines has numerous potential uses in oncology drug discovery and development. Characterisation of genes expressed in tumours may allow tumours to be separated into subsets defining subtypes that have a distinctive pathway utilisation. The molecular entities comprising the pathways which distinguish one disease subset from another then become potential candidate drug targets. Alternatively, gene expression patterns may be correlated with the degree of antiproliferative effect of candidate drug leads. This can reveal aspects of the drug's action that could serve to provide a further basis for benchmarking the generation of analogues or provide important information about pathways potentially modulated by the drug in achieving cytotoxicity. New information is emerging that the expression of drug transport-related molecules is a major variable that can be usefully explored using gene expression data, and the features promoting successful drug handling by the tumour cell may be an additional variable which can be illuminated by gene expression studies.

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http://dx.doi.org/10.1016/j.ejca.2004.08.006DOI Listing

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