The Genomics & Bioinformatics Group (GBG) is undertaking what has been characterized by others as a forerunner of the NCI/NHGRI Human Genome Atlas project. Whereas that project currently aims at molecular profiling of clinical tumors at the DNA and RNA levels, the GBG's work aims at a broader profiling at the DNA, RNA, protein, metabolomic, functional, and pharmacological levels - but in the logistically simpler, more homogeneous, more reproducible context of human cell lines, rather than clinical tumors. More specifically, we have established a set of collaborations for molecular profiling of selected drug-resistant cell lines and also the panel of 60 human cancer cell lines (the NCI-60) used by the NCI Developmental Therapeutics Program to screen >100,000 compounds and natural products for anticancer activity. The ultimate aim is to discover new drugs and biomarkers for targeted, personalized treatment of cancer. In service to that aim, we are also 'setting the table' for other researchers by producing molecular profile databases and bioinformatic software tools that are being used by thousands of laboratories around the world. That is, we are providing infrastructure for post-genomic biomedical research at the same time as we are pursuing translational goals related drugs and biomarkers for personalization of cancer therapy.That enterprise yields a number of types of contributions:-Molecular profile databases used by large numbers of laboratories and investigators (4 of our publications presenting the data have each generated >450 literature citations to date).-Bioinformatic computer tools and resources (the Miner Suite) that we originally programmed because we needed them but that we also make freely available on our web site (http://discover.nci.nih.gov). The manuscript on one of those tools (GoMiner) was cited in the literature >100 time in the past year, and the site receives about 5 million hits/year.-Translationally significant results derived from a combination of 'integromic' molecular profiling studies and the bioinformatic developments. Five of those findings with clinical implications have been (i) biomarkers to distinguish colon from ovarian tumors of unknown origin, (ii) asparagine synthetase as a predictor of ovarian cancer cell response to L-asparaginase; (iii) the """"""""Permissive-Apoptosis Resistance"""""""" (PAR) two-step model for development of acquired drug resistance; (iv) 'MDR1-inverse' compounds more active in cancer cells that express MDR1; (v) critical evidence in the 1990's that led to clinical development of oxaliplatin, now a 'standard-of-care' agent for treatment of colon cancer.Tangible results of this project in FY06 have been-26 manuscripts submitted and/or published, including 6 for Nature or Nature journals (3 of them published; 3 other that have passed editorial review so far).-3 NIH patent applications and one additional Employee Invention Report-A Director's Innovation Award-4 Federal Technology Transfer Awards-Launching of a new series of articles under the rubric """"""""Spotlight on Molecular Profiling"""""""" in the AACR's Molecular Cancer Therapeutics journalExperimental accomplishments in FY06:-Completion of microRNA profiling of the NCI-60 and DU145/RC0.
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