Gene expression microarray analysis in cancer biology, pharmacology, and drug development: progress and potential

With the imminent completion of the Human Genome Project, biomedical resear ch 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 gainin g increasingly widespread use as a means to determine the expression of pot entially all human genes at the level of messenger RNA. In this commentary, we review developments in gene expression microarray technology and illust rate the progress and potential of the methodology in cancer biology, pharm acology, and drug development. Important applications include: (a) developm ent of a more global understanding of the gene expression abnormalities tha t contribute to malignant progression; (b) discovery of new diagnostic and prognostic indicators and biomarkers of therapeutic response; (c) identific ation and validation of new molecular targets for drug development; (d) pro vision of an improved understanding of the molecular mode of action during lead identification and optimisation, including structure-activity relation ships for on-target versus off-target effects; (e) prediction of potential side-effects during preclinical development and toxicology studies; (f) con firmation 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 furthe r technological improvements and decreasing costs, the use of microarrays w ill become an essential and potentially routine tool for cancer and biomedi cal research. (C) 2001 Elsevier science Inc. All rights reserved.