By William J. LaRochelle, Richard A. Shimkets
An built-in evaluate of melanoma drug discovery and improvement from the bench to the sanatorium, exhibiting with large strokes and consultant examples the drug improvement procedure as a community of associated elements best from the chanced on goal to the final word healing product. Following a platforms biology technique, the authors clarify genomic databases and the way to find oncological goals from them, how then to increase from the gene and transcript to the extent of protein biochemistry, how subsequent to maneuver from the chemical realm to that of the dwelling mobile and, eventually, pursue animal modeling and medical improvement. rising melanoma therapeutics together with Ritux an, Erbitux, Gleevec Herceptin, Avastin, ABX-EGF, Velcade, Kepivance, Iressa, Tarceva, and Zevalin are addressed. Highlights comprise melanoma genomics, pharmacogenomics, transcriptomics, gene expression research, proteomic and enzymatic melanoma profiling applied sciences, and mobile and animal techniques to melanoma aim validation.
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9. Kerlavage A, Bonazzi V, di Tommaso M, Lawrence C, Li P, Mayberry F, et al. The Celera Discovery System. Nucleic Acids Res 2002; 30:129–136. 10. Overbeek R, Larsen N, Walunas T, D’Souza M, Pusch G, Selkov E Jr, et al. The ERGO genome analysis and discovery system. Nucleic Acids Res 2003; 31:164–171. 11. Hubbard T, Barker D, Birney E, Cameron G, Chen Y, Clark L, et al. The Ensembl genome database project. Nucleic Acids Res 2002; 30:38–41. 12. Karolchik D, Baertsch R, Diekhans M, Furey TS, Hinrichs A, Lu YT, et al.
ALTERNATIVES TO DIGITAL KARYOTYPING A recent improvement in the resolution of CGH was achieved by incorporating microarrays in the CGH analysis. Instead of hybridizing the tumor DNA to metaphase spreads of normal cells, the DNA is hybridized to BAC (bacterial artificial chromosome) 28 Hermeking Fig. 5. SAGE analysis of cancer-specific alterations in gene expression and copy-number changes. Flowchart showing the possible steps and outcomes of a SAGE-based analysis of cancer cell genomes and transcriptomes.
However, because of the low resolution of CGH, only a small number of oncogenes were identified via this route. One example is PIK3CA (14). In the future, array-CGH (also referred to as matrix-CGH), which promises to have a resolution up to 50 kbp, will presumably aid in the identification of genomic amplifications and the critical proto-oncogenes involved. However, a number of technical problems have to be overcome before this technique becomes widely used (25). Another approach used for the identification of oncogenes is RDA (representational difference analysis) (26).