Wednesday, March 21

7:30-8:15 Breakfast Technology Workshop	Sponsored by
Dynamic Arrays for Real-Time qPCR  Michael Y. Lucero, EVP, Marketing, Fluidigm Corporation Fluidigm has introduced nanofluidic chips called dynamic arrays, which provide experiment density in a class with microarrays yet consume orders of magnitude less sample and reagents compared to microplates. Dynamic arrays have been introduced for real-time qPCR. Each chip accepts 48 cDNA samples and 48 TaqMan assays, creating 2,304 (48x48) parallel reactions. Dynamic arrays for real-time qPCR are a significant advance for gene expression analysis as they provide a highly efficient means to validate expression changes for a set of genes on samples from many individuals.

8:35-9:05 Pharmacogenomic Testing Algorithms for Optimizing Initial Warfarin Dosing
Alan Wu, Ph.D., Clinical Professor, Laboratory Medicine, University of California San Francisco
Warfarin is an anticoagulant drug used to reduce the risk of arterial and venous thrombosis. Blood testing for the prothrombin time (and International Normalized Ratio) is used to determine if the drug is effective. Because there are many variables that determine the optimum dose in an individual, the incidence of adverse events, e.g., bleeding, is high. Pharmacogenomic testing for genes that encode cytochrome P450 and vitamin K epoxide reductase can be used to optimize dosing. We have developed and tested pharmacogenomic algorithms in a diverse patient population on warfarin.

9:05-9:35 Blood Gene Expression in Patients with Major Depressive Disorder Treated with Citalopram
Jarlath M. H. ffrench-Mullen, Ph.D., Scientific Director, CNS Program, GeneLogic, Inc.
Major depression (MD) is a psychiatric disorder that affects 5-10% of the population and is considered the second leading cause of disability by the World Health Organization. Several studies have indicated the involvement of genetic factors in MD, which may also play a role in a patient’s response (responder) or non-response (non-responder) to antidepressant treatment. We are conducting a large-scale gene expression study in lymphocytes of drug-naïve depressed patients treated with Citalopram on the AffymetrixR U133 Plus 2 microarrays pre-(t=0) and post-treatment (t=1 and 8 weeks). At 8 weeks, a urine toxicology screen was performed and drug level was measured (HPLC) to determine compliance. Our findings show promise for the eventual determination of possible biomarkers for classification of responders and non-responders to antidepressant treatment.

9:35-10:05 Utility of Pharmacogenomics in the Identification of Biomarkers for Patient Selection and Effective Treatments for Psychiatric Disorders
Smita Price, Ph.D., Director, Psychiatry Research, Curidium Ltd.
Psychiatric disorders are complex and multifactorial and the underlying molecular mechanisms precipitating clinical presentation remain elusive. Several subtypes of each disorder exist and this heterogeneity is reflected in complex clinical diagnosis which can vary during the course of the disorder. For a large proportion of patients, existing drugs offer inadequate treatment. There is a clear need for better diagnostic and therapeutic approaches for psychiatric disorders. Curidium has employed a pharmacogenomic approach to identify not only causative disease mechanisms but also biomarkers to differentiate patient subpopulations for clinical trials and treatment. Application of Curidium’ s proprietary technology ‘Homomatrix’ to gene expression data from biological samples obtained from heterogeneous patient populations revealed subpopulations with unique ‘molecular signatures’ and distinct clinical phenotypes. These ‘molecular signatures’ present an innovative approach for biomarker development to select appropriate patient subpopulations to improve the efficiency of clinical trials and develop effective treatments.

11:00-11:30 Circulating Oncoproteins as Biomarkers for Targeted Therapies
Walter P. Carney, Ph.D., President, Oncogene Science, Bayer Diagnostics
In this presentation I will speak about a panel of four oncoproteins that have been shown to be circulating in normal individuals and cancer patients and that have relevance to major targeted therapies that are either approved or in clinical trials. We have developed ELISA tests for four oncoproteins which include HER-2/neu, EGFR, ras and MN. I will update the serum HER-2/neu story with data from metastatic breast cancer patients treated with either small molecule drugs such as Lapatinib or Mab based therapy such as Herceptin. In addition, I will present data related to the three other circulating oncoproteins, EGFR, ras and MN.

1:30-2:00 Validating the Cancer Biomarker Supply Chain
Charles Buck, Ph.D., Director of Operations, The Bindley Bioscience Center, Discovery Park at Purdue University
The NCI clinical proteomics technology assessment consortia (CPTAC) teams establish, evaluate and provide protocols for discovery and validation of clinically relevant cancer biomarkers. In this consortium, the Analytical Proteomics Team (APT) from Purdue and Indiana University has established robust and intersecting platforms for biomarker validation and discovery. These platforms span the 'biomarker supply chain' including patient identification, sample collection handling and distribution, cancer biology, analytical processes, and data collection, management, analysis and mining. Information emerging from the new NCI CPTAC program (awards announcements expected October 06), procedural recommendations and specific examples would be the subject for presentation at the conference.

2:00-2:30 Biomarkers, Biological Diversity, and Decision Making: What to Measure, What it Means, and Why it Has Value
Thomas Paterson, Senior Vice President, In Silico R&D, Entelos, Inc.
Current biomarkers do not provide an adequate means to distinguish high responders from low responders prior to treatment, or predict the long-term benefit from early response. This problem is even greater for novel therapies, where little or no clinical data are available. In complex diseases such as cardiovascular disease, type 2 diabetes, and rheumatoid arthritis, established and investigative biomarkers show varying degrees of correlation to clinical outcomes across multiple trials ­ tantalizing clues to the underlying diversity (both genetic and lifestyle) in the patient population. Preclinical models provide additional clues, but questions on how best to translate such findings to diverse patient populations remain. The value of any biomarker ultimately depends on its ability to clarify the biological diversity relevant to a therapy, and how that clarity can improve decision making throughout clinical development. This talk will outline methodologies and discuss case studies of how Entelos is using its virtual patient technology to not only link biomarkers to diversity to decision making, but to reverse those links to identify the most valuable biomarkers and biomarker patterns.

2:30-3:00 Biomarkers Validation in Preclinical Cancer Prevention Studies
Konstantin Christov, M.D., Ph.D., Associate Professor, Surgical Oncology, University of Illinois at Chicago
Biomarkers related to cell cycle progression, apoptosis and cellular senescence in preclinical chemoprevention studies with SERMs, aromatase inhibitors, retinoids, cell differentiation agents, EGF-R modulators and farnesyltransferase inhibitors will be reviewed. A correlation will be made between the alterations in biomarkers and the clinical response in corresponding clinical trials. Future directions in biomarkers validations studies in preclinical and clinical settings will be discussed.