Gene expression microarray analysis in cancer biology, pharmacology, and drug development: progress and potential.
With the imminent completion of the Human Genome Project, biomedical research is being revolutionised by the ability to carry out investigations on a genome wide scale. This is particularly important in cancer, a disease that is caused by accumulating abnormalities in the sequence and expression of a number of critical genes. Gene expression microarray technology is gaining increasingly widespread use as a means to determine the expression of potentially all human genes at the level of messenger RNA. In this commentary, we review developments in gene expression microarray technology and illustrate the progress and potential of the methodology in cancer biology, pharmacology, and drug development. Important applications include: (a) development of a more global understanding of the gene expression abnormalities that contribute to malignant progression; (b) discovery of new diagnostic and prognostic indicators and biomarkers of therapeutic response; (c) identification and validation of new molecular targets for drug development; (d) provision of an improved understanding of the molecular mode of action during lead identification and optimisation, including structure-activity relationships for on-target versus off-target effects; (e) prediction of potential side-effects during preclinical development and toxicology studies; (f) confirmation of a molecular mode of action during hypothesis-testing clinical trials; (g) identification of genes involved in conferring drug sensitivity and resistance; and (h) prediction of patients most likely to benefit from the drug and use in general pharmacogenomic studies. As a result of further technological improvements and decreasing costs, the use of microarrays will become an essential and potentially routine tool for cancer and biomedical research.
Clarke
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Cancer Research Campaign Centre for Cancer Therapeutics, E Block, Institute of Cancer Research, 15 Cotswold Road, SM2 5NG, Sutton, Surrey, UK.
te Poele
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Wooster
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Workman
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D000818:Animals; D015195:Drug Design; D005544:Forecasting; D020869:Gene Expression Profiling; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010600:Pharmacology / Q000639:trends; D012333:RNA, Messenger / Q000096:biosynthesis
D012333:RNA, Messenger