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Novel Cancer Biomarkers
May 20, 2009
12:00 p.m. – 2:00 p.m. EST

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12:00-12:10 Chairperson's Opening Remarks

12:10-12:35 Non-codingRNAs as Biomarkers in Human Cancers
George A. Calin, M.D., Ph.D., Associate Professor, Experimental Therapeutics & Cancer Genetics, The University of Texas, M.D. Anderson Cancer Center
MicroRNA alterations are involved in the initiation, progression and metastases of human cancer. The main molecular alterations are represented by variations in gene expression, usually mild and with consequences for a vast number of target protein coding genes. The causes of the widespread differential expression of miRNA genes in malignant compared with normal cells can be explained by the location of these genes in cancer-associated genomic regions, by epigenetic mechanisms and by alterations in the microRNA processing machinery. MicroRNA expression profiling of human tumors has identified signatures associated with diagnosis, staging, progression, prognosis and response to treatment. In addition, profiling has been exploited to identify microRNAs genes that may represent downstream targets of activated oncogenic pathways or that are targeting protein coding genes involved in cancer. Recent studies proved that miRNAs are main candidates for the elusive class of cancer predisposing genes and that other types of non-codingRNAs participate in the genetic puzzle giving rise to the malignant phenotype. These discoveries could be exploited for the development of useful markers for diagnosis and prognosis, as well as for the development of new RNA-based cancer therapies.

12:35-1:00 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.

1:00-1:10 Sponsored Presentation
Opportunity available. Contact Ilana Quigley, Business Development, 781-972-5457 or iquigley@healthtech.com.

1:10-1:35 Cancer Biomarker Discovery in the Context of Individualized Medicine
Josip Blonder, M.D., Senior Research Scientist, Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick Inc., NCI-Frederick
There is growing consensus that personalized medicine may significantly improve the outcome of a patient diagnosed with cancer.  Thus, individualized proteomic approaches facilitating biomarker discovery from clinically relevant specimens are critically needed.  The objective of our study was to determine whether tumor-derived proteins are detectable by biological mass spectrometry in peripheral blood of a patient diagnosed with cancer and their potential utility as disease-specific biomarkers. Tumor, normal adjacent tissue and preoperative plasma were obtained from a single patient diagnosed with renal cell carcinoma (RCC). Subtractive proteomic analysis of proteins identified within tissue specimens revealed a subset of 202 proteins identified exclusively in tumor. Of these, eight proteins were identified in the plasma by meeting the following four criteria: not identified in normal-adjacent tissue, identified in tumor, identified in plasma, and exhibiting a higher spectra count in tumor versus plasma. Using Western-blot analysis we confirmed the presence of Cadherin-5 in the patient’s preoperative plasma while its presence was not detected in the plasma of a matched healthy donor nor in the ovarian cancer (SKOV-3) and prostate cancer (LNCaP) cell lysates. Our experiments provide the evidence that in-depth subtractive tissue-directed proteomic analysis is capable of identifying tumor-derived marker proteins in peripheral plasma of a single patient diagnosed with cancer. Our findings also suggest an active role of cadherin-5 in the RCC molecular-phenotype of our patient under study. 

1:35-2:00 Metabolomics-derived Biochemical Markers of Prostate Cancer Aggressiveness
Jeffrey Shuster, Ph.D., Director, Diagnostics Development, Metabolon, Inc.
The elucidation of the complex molecular and physiological events that characterize the differences between normal cells and cancer cells is under intense investigation both at the research level and in clinical practice. A large number of studies have been reported with DNA, RNA, and protein-based technologies, however, few studies have been performed to characterize cancer at the biochemical level.  It is by gaining this type of mechanistic understanding of a disease that researchers will unlock the keys to discovering new diagnostics. This webcast presentation will provide an overview of a study undertaken to better understand and profile the biochemical changes associated with prostate cancer aggressiveness. Using metabolomics, a global biochemical profiling technology, tissue, urine and plasma samples were analyzed enabling researchers to identify a series of biochemicals (including sarcosine) that are key potential predictors of cancer aggressiveness. Attendees will learn about this study as well as how the underlying technology that fueled this discovery is being applied in hundreds of other areas – like diabetes, drug safety research and even to gain a better of understanding of consumer goods products.


About the Speakers:

George A. Calin, M.D., Ph.D., Associate Professor, Experimental Therapeutics & Cancer Genetics, The University of Texas, M.D. Anderson Cancer Center
George Adrian Calin received both his M.D. and Ph.D. degrees at Carol Davila University of Medicine in Bucharest, Romania.  After working cytogenetics as undergraduate student with Dr. Dragos Stefanescu in Bucharest, he completed a training program in cancer genomics in Dr. Massimo Negrini’s laboratory at University of Ferrara, Italy. In 2000 he became a postdoctoral fellow at Kimmel Cancer Center in Philadelphia, PA, in Dr. Carlo Croce’s laboratory.  He is presently an Associate Professor in Experimental Therapeutics at MDACC and studies the roles of microRNAs and other non-coding RNAs in cancer initiation and progression, as well as the mechanisms of cancer predisposition and explores new RNA therapeutic options for cancer patients.

Shannon Payne, Ph.D., Senior Scientist, Epigenomics, Inc.
Shannon Payne received her Ph.D. degree for research on the somatic genetics of BRCA1 in 2000 from the University of Washington Genetics Department under the direction of Dr. Mary-Claire King.  In the same year, Dr. Payne was awarded a Postdoctoral Fellowship in Cancer Biology at the Fred Hutchinson Cancer Research Center in Seattle, WA.  Her advisor was Christopher J. Kemp, Ph.D., one of the most prominent researchers in the field of tumor suppressor haploinsufficiency. There Dr. Payne developed a novel hypothesis to explain the prognostic significance of cyclin dependent kinase inhibitor p27 in gastrointestinal cancer and collaborated in the development of a small animal PET imaging system.

In 2006, Dr. Payne was offered a position as an Assay Development Scientist at Epigenomics, Inc. Currently she is a Senior Clinical Scientist advising the PRESEPT clinical trial at Epigenomics, Inc. Dr. Payne has authored and co-authored multiple publications and filed five patent applications. Her current research interests include the design of biomarker clinical trials for bias prevention, the development of real time PCR for quantitative analysis of DNA methylation biomarkers and the discovery of prognostic cancer biomarkers.

Josip Blonder, M.D., Senior Research Scientist, Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick Inc., NCI-Frederick
Josip Blonder received his M.D. degree in 1978 from the School of Medicine Rijeka, Rijeka University Croatia. He was a practicing physician until he moved to U.S. in 2000.  In 2001, Dr. Blonder was awarded a Postdoctoral Fellowship in Proteomics through Associated Western Universities at Pacific Northwest National Laboratory (PNNL), Richland, WA. His advisor was Richard D. Smith, Ph.D., one of the most prominent scientists in proteomics. There Dr. Blonder developed a method for analysis of membrane proteins using LC-MS/MS.  In 2002, Dr. Blonder was offered a position in the Laboratory of Proteomics and Analytical Technologies (LPAT), SAIC-Frederick Inc, at the NCI-Frederick.  Currently, he is the Head of Quantitative and Clinical Proteomics at the LPAT. Dr Blonder has authored and co-authored over 30 articles, and filed several patent applications. His current research interests include the development of mass spectrometry techniques for quantitative analysis of membrane proteins and cancer biomarker discovery.

Jeffrey Shuster, Ph.D., Director, Diagnostics Development, Metabolon, Inc.
Dr. Shuster received his Ph.D in genetics from the University of Washington, Seattle, studying the yeast cell cycle under Dr. Lee Hartwell.  He joined Metabolon as director of diagnostics development in 2008. Prior to Metabolon, Dr. Shuster served as president of an entrepreneurial start-up diagnostics company, Teotten Diagnostics, aimed at diagnostics of hospital acquired infections.  His experience also includes technical management and business development at Paradigm Genetics, work with Novo Nordisk (now Novozymes) in the applications of biotechnology to the production of industrial enzymes as well as expertise in diagnostics for Hepatitis C and HIV AIDS with Chiron Corporation (now Novartis). Dr. Shuster has over 40 scientific publications and over 30 issued patents.


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