Gene expression microarray technologies in the development of new therapeutic agents.
We review in detail how gene expression microarray technology is benefiting all phases of the discovery, development and subsequent use of new cancer therapeutics. Global gene expression profiling is valuable in cancer classification, elucidation of biochemical pathways and the identification of potential targets for novel molecular therapeutics. We exemplify the value in tissue culture and animal models of cancer, as well as in clinical studies. The power of expression profiling alongside gene knockout or knockdown methods such as RNA interference is illustrated. The use of basal or constitutive gene expression profiling to understand and predict drug sensitivity or resistance is described. The ability of expression profiling to define detailed molecular signatures of drug action is emphasised. The approach can identify on-target and off-target effects. It can be used to identify molecular biomarkers for proof of concept studies, pharmacodynamic endpoints and prognostic markers for predicting outcome and patient selection.
Clarke
Paul A
PA
Cancer Research UK Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey SM2 5NG, UK.
te Poele
Robert
R
Workman
Paul
P
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004249:DNA Damage / Q000187:drug effects; D015195:Drug Design; D005544:Forecasting; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010597:Pharmacogenetics
D000970:Antineoplastic Agents