Role of genomics in identifying new targets for cancer therapy.
The detailed map of the human genome can potentially transform future cancer therapy by merging genomics with pharmacology, thereby identifying which patients will benefit from specific therapeutic agents. Single-nucleotide polymorphisms (SNPs) provide a valuable tool for this pharmacogenetic approach to cancer therapy. The discovery of SNPs as disease markers may facilitate identification of populations at increased risk for certain cancers. In addition, SNP genetic screening may facilitate administration of appropriate treatment modalities or reveal specific genetic profiles that have importance in drug efficacy and toxicity. In addition to SNP analysis, DNA and tissue microarray analyses have the potential to transform the future of cancer therapy. For example, DNA microarrays may improve tumor classification systems as well as provide a molecular level dissection of global gene expression changes that occur in carcinogenesis. Tissue microarrays would allow one to verify candidate genes, identified from DNA microarrays, against archival tumor specimens with known clinical outcome. In addition, both microarray technologies may be combined to rapidly validate gene targets. We will review and discuss these state-of-the-art technologies including data suggesting that the combined use of these high throughput technologies will facilitate our understanding of the genetic complexities inherent in cancer and will revolutionize cancer therapy.
Anzick
Sarah L
SL
Division of Intramural Research, Cancer Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892-8002, USA.
Trent
Jeffrey M
JM
D015195:Drug Design; D020869:Gene Expression Profiling; D014644:Genetic Variation; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*