Novel Cancer Biomarkers

Venue: San Diego

Location: San Diego, California, United States

Event Date/Time: Jan 26, 2009 End Date/Time: Jan 26, 2009
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Novel Cancer Biomarkers
9:00-9:05 Chairperson’s Opening Remarks

9:05-9:30 in vivo Discovery and Validation of Biomarkers of Human Drug Response and Resistance
Joerg Heyer, Ph.D., Principal Scientist, Group Leader, Genetic Models, AVEO Pharmaceuticals, Inc.
With the emerging elucidation and understanding of the human genome, the complexities of genetic changes in cancer have become apparent. Traditional models of preclinical research and development have generally not recapitulated the dynamics of the genome found in cancer. New approaches to genetically engineered models, i.e. exploiting the natural diversity of signaling pathways in genetically engineered cancer models, or generating spontaneous human tumors in tissue transplantation models, have shown great promise to faithfully capture the complexity of genomic changes seen in cancer. We have generated a Human Response Prediction approach, based on naturally occurring variation in our genetically defined models of cancer, which allows us to identify genetic biomarkers of therapeutic response.

9:30-9:55 Preclinical Biomarker Discovery and Validation for a Small Molecule Inhibitor of MEK Kinase
Mark R. Lackner, Ph.D., Scientist, Developmental Oncology Diagnostics, Genentech, Inc.
Abstract unavailable at the time of printing.

9:55-10:20 Development of Clinically Relevant Gene Expression Profiles for Prognosis of Early Stage Breast Cancer
Richard Bender, M.D., FACP, Vice President and Chief Medical Officer, Agendia, Inc.
Gene Expression Profiling is rapidly becoming the new frontier for the development of biomarkers for the diagnosis of disease, for the assessment of prognosis and for the prediction of the likelihood of responding to a particular drug or class of drugs. The ability to analyze patient groups with multi-gene profiles using either RT-PCR or microarray oftentimes belies the complexity of the clinical question and is subject to over-fitting the data, as many genes are used to discriminate between 2 groups of patients , oftentimes simply responders or non-responders, "low" risk or "high" risk or disease present or absent groups. As such, meticulous attention to all experimental details from extraction of genomic material from patient specimens to interpretation of gene expression, must be rigidly controlled. As interpretation of the multi-gene readout is not "intuitive" to the ordering physician (unlike a single analyte assay, such as CA 27-29) requiring a "black box" mathematical algorithm to generate or risk profile or result, the FDA has issued IVDMIA Guidance for the Industry suggesting how these assays need to be regulated. The presentation will discuss the process of assay development for breast cancer prognosis as a way of illustrating the key steps in this process and will review the latest developments in governmental oversight.

10:20-10:40 Networking Coffee Break

10:40-11:05 Circulating HER-2/neu, A Biomarker for HER-2 Positive Breast Cancer, from Discovery to Patient Management
Walter Carney, Ph.D., Head, Oncogene Science, Siemens Healthcare Diagnostics, Inc.
Pharmaceutical companies are developing a large number of targeted oncology therapies that will require specific biomarker tests or targeted diagnostics to guide the use of these agents. This presentation will provide an overview and update on the serum HER-2/neu test, which is a specific biomarker for HER-2 positive breast cancer. The serum HER-2/neu test measures the extracellular domain (ECD) of the HER-2/neu oncoprotein in the blood of breast cancer patients. The test is used clinically to measure the rise and fall of the ECD which parallels clinical course of disease. Since the test specifically measures the circulating ECD, it is used to monitor the response or lack of response of the HER-2 positive tumor exposed to a variety of therapies, including hormone therapy, chemotherapy, and Herceptin/chemotherapy of Tykerb monotherapy.

11:05-11:30 Discovery of miRNA-Based Biomarkers for Cancer
Søren Møller, Ph.D., Vice President, Research and Development, Exiqon A/S
Abnormal expression of microRNAs (miRNAs) in cancer implies that these small ~22-nucleotide molecules play a role in oncogenesis. Therefore miRNAs may comprise a novel class of diagnostic and prognostic signatures. This talk will focus on examples of using microRNA for cancer classification, prognosis and treatment selection.

11:30-12:30 pm Lunch on your own

12:30-12:55 Cancer Biomarker Discovery in the Context of Personalized Medicine
Josip Blonder, M.D., Senior Research Scientist, Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick Inc., NCI-Frederick
The major goal of oncoproteomics is the discovery of clinically relevant molecular biomarkers. So far, the translation of proteomic assays to applicable diagnostic and/or prognostic tests in clinical oncology and personalized medicine has been disappointing. We developed an innovative proteomic platform for cancer biomarker discovery that is amenable to personalized medicine since all specimens were obtained from a single patient, diagnosed with renal cell carcinoma. This approach relies on concurrent profiling of peripheral serum/plasma specimens obtained prior to surgery coupled with subtractive analysis of non-tumorous and tumorous tissue samples procured after the surgical intervention. Multidimensional shotgun proteomic analysis, rigorous bioinformatic data processing coupled with orthogonal validation was employed to narrow the selection/panel of potential renal cancer biomarker proteins.

12:55-1:20 Industrialized Proteomics for the Discovery and Validation of Oncology Biomarkers
Daniel Chelsky, Ph.D., Chief Science Officer, Caprion Proteomics
The success of many investigational drugs is dependent on matching treatments with the appropriate target populations. Variability in response to therapy, both with regards to efficacy and to adverse events, is leading the pharmaceutical industry down the path of personalized medicine. Further pushing the process along are government and private insurance payors who are faced with very expensive treatments that can help some but provide little benefit and possible harm to others. One promising solution to the problem is to identify predictive biomarkers of drug efficacy; circulating proteins that stratify patients into populations of likely responders and non-responders to a proposed therapy. Finding such biomarkers has been challenging due to the complexity of human plasma, the sample of choice, and to the available technologies for detection and quantification of thousands of proteins. Based on the experience of over two dozen preclinical and clinical proteomic studies with pharmaceutical partners, an “industrialized” and very productive approach to biomarker discovery and validation has been developed. Results from multiple oncology biomarker discovery studies will be presented that make the case for accelerating the move to personalized medicine.

1:20-1:45 Metabolite Biomarkers of Prostate Cancer Aggressivity
Jeffrey Shuster, Ph.D., Director, Diagnostics Development, Metabolon, Inc.
Even with all the diagnostics methods in use today, it is difficult to determine with surety which prostate cancers are indolent, and which are aggressive and have the potential to metastasize. Diagnostic tests that distinguish indolent from aggressive tumors have the potential to reduce the number of unnecessary biopsies and prostatectomies. Prostate cancer aggressivity was investigated at the biochemical level using metabolomics with urine from men at-risk for prostate cancer, and from post-surgical prostate tissue. The results identified sets of mechanism-based biomarkers correlated with prostate cancer aggressivity. In this talk, we will briefly describe the metabolomics platform and its utility for developing cancer diagnostics.

1:45-2:10 Networking Refreshment Break

2:10-2:35 From Discovery to the Clinic: The Novel DNA Methylation Biomarker, Septin 9, for the Detection of Colorectal Cancer in Blood
Shannon Payne, Ph.D., Senior Scientist, Epigenomics, Inc.
Detection of colorectal cancer (CRC) at early stages has been shown to greatly decrease mortality from the disease. Availability of a blood-based test for CRC is expected to improve screening compliance in the general population. Through DNA methylation-sensitive, restriction enzyme-based biomarker discovery we identified a region of the Septin 9 gene that is methylated in over 90% of colorectal cancer tissues with little or no methylation in normal colon tissue and other controls. Using a systematic method of biomarker development, we demonstrated specific detection of CRC DNA using the Septin 9 methylation biomarker in multiple studies of plasma from CRC patients and controls. A prospective clinical trial is now underway to determine the clinical performance of the Septin 9 biomarker in the CRC screening-eligible population.

2:35-3:00 Multiplexed Analysis of Glycan Variation on Serum Proteins Using An Antibody Array for Biomarker Profiling
Bryce P. Nelson, Ph.D., Vice President, Research and Development, Gentel Biosciences
Protein glycosylation is a critical determinant of protein function, but there is a lack of tools for discovery and validation of the glycosylation of specific proteins for use as biomarkers. We have developed a 46-plex antibody array in a 96-well format to measure changes in both the glycosylation and concentration of specific cancer biomarker proteins in patient serum samples. To do this, an array of antibodies captures specific proteins from serum and the glycosylation of captured proteins is measured using one of eight unique biotinylated lectins. Chemical derivatization of the glycans on the spotted antibodies prevents lectin binding to those glycans. Relative abundance of serum proteins is measured on a separate antibody array after labeling with a universal conjugate. By profiling both protein and glycan variation in multiple serum samples using parallel protein abundance and glycan-detection assays, new disease-associated glycan alterations can be identified and validated for use as biomarkers.

3:00 Close of Workshop