The role of emerging genomics and proteomics technologies in cancer drug target discovery.
Cancer drugs have traditionally been identified in screens designed to produce broad biological end points such as cell death. A serious undesired outcome of drugs discovered in these screens is that the mechanism of drug action is unknown and such drugs often have adverse side effects. Designing cancer drugs that act on specific targets offer the advantage that the mechanism of drug action can be understood and accurately monitored in clinical trials leading to development of better drugs. The pharmacological industry has recently shifted to a target directed drug discovery model. However, until recently potential cancer drug targets comprised of only a small fraction of the human genome. The human genome project and high-throughput structural and functional genomics have dramatically increased the number of cancer drug targets. Deciphering cancer drug targets requires the understanding of biochemical pathways that are affected in the cancer genome. It has been suggested that utilization of Single-nucleotide polymorphisms (SNPs) will aid in identifying individuals at high risk of developing certain cancers, and will also help in development of tailored medication or identify genetic profiles of specific drug action and toxicity. Achieving successful new cancer drug development schemes will require a merger of research disciplines that include pharmacology, genomics, comparative genomics, functional genomics, proteomics and bioinformatics. In this review the significance and challenges of these rapidly evolving technologies in cancer drug target discovery are discussed.
Onyango
Patrick
P
Department of Medicine, Johns Hopkins University School of Medicine, 1064 Ross, 720, Rutland Avenue, Baltimore, MD 21205, USA. Onyango@jhmi.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019295:Computational Biology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D023381:Endpoint Determination; D023281:Genomics; D005838:Genotype; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040901:Proteomics; D012334:RNA, Neoplasm / Q000235:genetics
D000970:Antineoplastic Agents; D012334:RNA, Neoplasm