Analysis of a large amount of data generated from genomic and proteomic assays for cancer has become the bottleneck in deriving the conclusion from these experiments.
 Biophase Systems utilizes proprietary in silico approaches to integrate disparate and distributed data to expand our understanding of the mechanistic details of the diseases. The software, SIMUSITE (http://www.biophase.net/simusite), efficiently enables the analysis of such data. The software is created to provide a prediction of drug response and utilization of experimental data in different therapeutic contexts. In addition, the software system is architected with caBIG (http://cabig.nci.nih.gov) standard by employing the caBIGidentified critical Minimum Data Elements (MDE) and Common Data Elements (CDE) across caBIGtools. The system helps create integration of data obtained from different technologies and enables integrated analysis of the drug effect in the context of public domain studies conducted at NCI, and other affiliated research institutions.
 Clinical studies aimed at treating Chronic Myelogenic Leukemia (CML) with the natural product alkaloid Homoharringtonine (HHT) [omacetaxine mepesuccinate- USAN/INN designation] have produced encouraging results for patients with CML resistant to tyrosine kinase inhibitor therapies. HHT has been shown to be an effective inhibitor of proteins synthesis (via inhibition of the elongation step of polypeptide synthesis) and to induce apoptosis and inhibit angiogenesis.
 To further understand the target of HHT treatment, K562 leukemia cell line exposed to 10nM HHT for 0.5, 1, 4 and 8 hr, was examined for phosphorylation assays. There was a significant influence on CREB pathway suggesting selective activation and deactivation of a large number of MAPkinase dependent pathways in contrast to previously reported imatinib mesylate. Additionally, protein levels of BCR-ABL (oncoprotein for CML phenotype), Mcl-1 (anti-apoptotic protein) and Hsp-90 (chaperone protein which stabilizes oncoproteins such as BCR-ABL) were also found to be reduced in cells treated with HHT for 48 hrs.
 These data transformed with MDE and CDE are being analyzed with SIMUSITE to elucidate the regulatory pathways with specific emphasis on transcription factors and their downstream targets. The analysis will also involve comparing the public domain data related to imatinib mesylate treatment to further enrich the parametric comparisons between both the drugs. This will potentially help uncover the direct link between the HHT treatment and cytotoxic response of K562 cells implicating ultimate mechanism of action in CML therapy using HHT.

99th AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA