[Polygenetic pharmacogenomic strategies to identify drug sensitivity biomarkers].
Pharmacogenomics is a large-scale systematic approach using a variety of genomic technologies to discover drug response determinants and promote a better understanding of the genetic and molecular basis underlying variable drug response among patients. However, few critical prediction markers of drug response have been validated to date. Drug sensitivity is determined by multiple genes:drugs are often involved in complex metabolic pathways before they produce anti-cancer activity, and the related genes do not act in isolation. Although the worldwide research on the human genome exerts a major impact on medical science and advanced medicine, the detailed function and interaction of most genes remain unclear. There is clear evidence that a variety of genes are closely associated with cellular drug sensitivity, but most of the regulatory mechanisms of their expressions are poorly understood. To understand the drug sensitivity mechanism and identify the key biomarkers, recent attention has focused on the transcriptional mechanisms of drug sensitivity genes and their network. These approaches in genome research and the functional analysis may revolutionize the anticancer chemotherapy world. The possible contribution of new challenges and problems of the day were reviewed while showing recent findings on the analyses of 5-FU metabolic pathway and the key gene DPYD as an example.
Nishiyama
Masahiko
M
Dept. of Translational Cancer Research, Research Institute for Radiation Biology and Medicine, Hiroshima University.
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010597:Pharmacogenetics
D000970:Antineoplastic Agents; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil