Molecular Medicine Tri-Conference February 27-March 2, 2007
Pathway Analysis: Road Maps Through the Genome February 28-March 2, 2007
San Francisco, CA
9:00 am - 12:00 pm
microRNA Assay Tools Short Course (SC6)
Keld Sorensen, Ph.D., Director R&D, Luminex Corp.
WEDNESDAY, FEBRUARY 28
8:10 Clinical Qualification and Acceptance of Biomarkers and Surrogate Endpoints
Steven A. Williams, M.D., Ph.D., Executive Director & Worldwide Head, Clinical Technology & R&D, Pfizer Inc.
Biomarkers are fundamental to our understanding of disease, to the measurement of response to therapy and to clinical management of patients. It is therefore surprising that there is considerable uncertainty around what evidence of clinical qualification is required for a biomarker to be used and accepted by drug developers, regulators and the medical community. Key factors that influence acceptance will be discussed along with approaches to overcoming the uncertainty.
11:10 Dissecting Activities of Kinase Inhibitors with RNA Profiling, Dose-Response Study Designs, and Pathway Analysis
Nathan Siemers, Ph.D., Director of Bioinformatics, Bristol-Myers Squibb Co.
11:30 The New Kid on the Block: microRNA Profiling in Cancer from a Bioinformatics Perspective
Yuriy Gusev, Ph.D., Assistant Professor, Department of Surgery, Adjunct Assistant Professor, Institute for Breast Health, Co-Director, Bioinformatics Core Facilities, OU Cancer Center, University of Oklahoma
Global expression profiling of microRNAs in human tumors has recently provided new and sometimes controversial insights into the new level of regulation of gene expression in cancer. Aberrant microRNA expression patterns in human cancers may offer new clues to mechanisms of tumorigenesis and may provide diagnostic biomarkers for cancer diagnostics. However the exact mechanisms and role of microRNA in cell signaling and regulation of gene expression are not well understood. It presents new challenges for bioinformaticians trying to incorporate this previously unknown level of regulation into existing paradigm of pathways and gene interaction networks. Recent results of our analysis of microRNA expression in human cancer cell lines and in pancreatic tumors will be presented and discussed from bioinformatics perspective.
11:50 Detecting Altered Expression and Activation of Signaling Pathways in Cisplatin Resistant Ovarian Cancer
William Ricketts, Ph.D., Director of Research, Oncotech Inc.
The determination of drug resistance patterns for a tumor is important for selecting efficacious therapies and minimizing side effects from drugs to which tumors will not respond. In addition, understanding the signaling pathways that contribute to the resistant phenotype or provide the tumor with a growth advantage may also expose potential therapy choices. The Extreme Drug Resistance (EDR) Assay? is a clinically validated assay used to test tumors for drug resistance. Based on response in the EDR assay, tumors are segregated into three groups: extreme drug resistant (EDR), intermediate drug resistant (IDR), and low drug resistant (LDR). In this study a set of ovarian tumors, including each Cisplatin drug response, were selected from chemotherapy na?ve patients with LDR response to all other drugs tested. These tumors had also been analyzed on Affymetrix gene arrays. The gene array data was analyzed using PathArt by Biosys. A set of proteins identified by PathArt as being overexpressed in Cisplatin resistance were analyzed for protein expression. The analyses of the gene array data and protein expression supported the activation of these pathways and provided additional pathways to be examined. These types of data provide insight into drug resistance and may assist selection of more efficacious second line therapies based on tumor specific pathway profiling.
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