Day 1 | Day 2
Biomarkers have been a mainstay of modern medicine: identifying that physical or biochemical change in the body that indicates an effective treatment or cure. With new initiatives from regulators to have biomarker assays available as drugs are developed, the role of biomarkers has shifted. The Inaugural Translational Biomarkers will showcase the latest in translatable biomarkers (pharmacodynamic, predictive, prognostic, toxicological and diagnostic). Animal models have been used for decades in pharmaceutical research, but with limited success for direct prediction in man. Experts will identify both models and strategies for using biomarkers that will create correlations, predictions and translation to the clinic.
RECOMMENDED SHORT COURSES*
(SC3) Novel Cancer Biomarkers
(SC5) Biomarker Qualification and Validation
(SC7) Planning Biomarker Development: Aligning Strategy, Science, and Technology
*Separate registration required
THURSDAY, SEPTEMBER 8
12:30 pm Conference Registration
1:30 Chairperson’s Opening Remarks
Suso Platero, Ph.D., Director, Oncology Biomarkers, Centocor, Ortho Biotech Oncology R&D, unit of J&J PRD LLC
1:40 Evolving Laboratory Technologies to Assess Predictive and Prognostic Biomarkers: Potential Utility vs. Challenges
Abdel Halim, Pharm.D., Ph.D., DABCC-CC, DABCC-TOX, DABCC-MD, FACB, Director, Clinical Biomarkers, Daiichi Sankyo Pharma Development
Biomarkers have been playing a critical role in patient management and pharmaceutical trials as diagnostic, prognostic, predictive, and drug efficacy indicators. Technologies like genotyping, gene expression, proteomics, immunohistochemistry, and in-situ hybridization become more and more important tools to evaluate biomarkers. Classical sample-substitute, e.g. CTC and cell-free plasma DNA is gaining attraction and fame in the field. However, without proper assessment and consideration of related challenges and pitfalls, biomarkers could be misleading rather than beneficial. This presentation will address potential benefits versus risk of biomarker applications especially in relation to evolving technologies.
2:10 Applying Genomic Platforms to Generate Unbiased Responder and Treatment Hypotheses for Oncology Translational Research
Jing Li, Ph.D., Head, Genomic Screening, Exploratory & Translational Science, Merck & Co.
The talk will be focused on using RNAi synthetic lethal screens and drug response screens in large panel of cancer cell lines to generate responder/resistance and drug treatment hypotheses for oncology translational research
2:40 Implementing Flow Cytometry Biomarker Assays in Clinical Studies
Dianna Wu, Director, Clinical Biomarkers & Diagnostics, Merck & Co.
The implementation of flow cytometric biomarker assays in clinical trials, especially global clinical trials, remains a challenge due to the limited stability of clinical specimens, lack of QC materials and the technical variations between analytical laboratories. We will summarize practice in validating and implementing flow cytometric biomarker assays in drug development.
3:10 qNPA Measurement of Fusion Genes
Charles Van Sant, Ph.D., Assistant Director, Pharmacodynamics, Astellas Global Development, Inc.
The quantitative nuclease protection assay (qNPA) technology permits rapid and accurate measurement of the presence and expression levels of genes, including fusion variants, in a wide range of sample types, including formalin, fixed paraffin embedded (FFPE) tissue making it ideal for translational and clinical application. The automated qNPA protocol requires no RNA extraction, no amplification, and no RNA labeling which have traditionally been problematic when using PCR-based and other technologies. qNPA methodology measures cross-linked RNA without the need to solubilize or reverse cross-linking. Thus, reliable measurements are independent of time in fixative or how long FFPE has been archived (e.g. 35+ years) in the case of retrospective studies. qNPA permits the measurement of the level of each gene and each of any number of known fusions as well as the identification of the presence of unknown fusions in a single assay. For instance measuring in one assay/array the following genes and fusions: ELM4-ALK V1, V2, V3a, V3b, V4, V5a, V5b, V6, V7, total EML4, total 3’ and 5’ ALK for unknown variant identification. An overview of the system and data on quantification of EML4/ALK and other fusions in clinical samples, matched frozen and fixed samples, and cell lines (PC9, A549, H358, H460, H2228, H2030, H3255, and H1650) will be presented, including the identification of multiple fusions within a sample and the identification of unknown fusions.
3:40 Networking Refreshment Break in the Exhibit Hall with Poster Viewing
4:20 CASE STUDY: Altered Expression of Insulin Receptor Isoforms in Breast Cancer
Jiaqi Huang, Ph.D., Pharmacogenomics, Translational Science, MedImmune
In response to blocking IGF1 and IGF2, dramatic levels of antitumor activity were observed in tumors that express both IGF1R and IR-A or IR-A. Furthermore, our results have identified the IR-A:IR-B ratio as a critical biomarker associated with the luminal-B breast cancer subtype. The use of the IRA:IRB ratio to guide patient selection for IGF-targeted therapy in breast cancer has the potential to provide significant clinical benefit to numerous cancer patients.
4:50 Standardization of Blood Biomarkers: Innovations through Automation
Denise L. Faustman, M.D., Ph.D., Director, Immunobiology, Massachusetts General Hospital; Associate Professor, Medicine, Harvard Medical School
In this presentation we demonstrate and quantify Ficoll’s inaccuracy in terms of viability, purity, and yield of PBLs. We then demonstrate the value of our newly improved method that automates and standardizes whole cell PBLs without the use of gradient technology. The new procedures uses paramagnetic particles attached to antibodies to detect cells of interest with a newly designed robotic platform. We demonstrate that this new method can reliably isolate an extremely rare subset of autoimmune PBLs (<1 x 10-6 of whole blood cells) largely responsible for select disease processes and allow standardzations of biomarkers for select immune diseases.
5:20 Molecular Biomarker Profiles of Ovarian Cancer Cells Obtained from Intraperitoneal Fluid, Lymph and Blood
Marek Malecki, M.D., Ph.D., Associate Professor of Genetics, Genomics, and Gene Therapy; Director, Biotechnology Program, Western University of Health Sciences
Ovarian cancer is the leading cause of deaths among all gynecological cancers. Identification of molecular biomarkers present on surfaces of cancer cells not only helps to diagnose cancer at the earliest stages, but also to proceed with development of personalized vaccine, immunotherapy, and/or targeted delivery of suicide gene therapy. We have recently developed a novel technology to determine ovarian cancer cell molecular profiles based upon superparamagnetic, genetically engineered single chain single chain variable fragments generated from the libraries of the patients’ B cells, which is followed by single cell arrays, sequencing, and analyzing their own antibody response profiles. This technology allows us to screen patients with instant broadcasting diagnosis and prognosis, while preparing therapies eliminating only cancer cells and leaving healthy cells unharmed.
5:50 Close of Day
6:30-9:00 Dinner Short Courses*
*Separate registration required
Day 1 | Day 2