Tuesday, May 5
7:00 am Conference Registration and Morning Coffee
8:00 Chairperson’s Opening Remarks
G. Mike Makrigiorgos, Ph.D., Professor, Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School
8:10 Talk Title to be Announced
Matthias Holdhoff, M.D., Ph.D., Assistant Professor, Oncology, Medicine and Neurosurgery, Brain Cancer Program, SKCCC, Johns Hopkins University
8:35 Detection of Somatic Mutations in Biological Fluids in the Management of Cancer
Nickolas Papadopoulos, Ph.D., Professor, Ludwig Center, SKCCC, Johns Hopkins University
Somatic mutations are cancer-specific biomarkers that reveal the presence of cancer when present in cell-free DNA or DNA derived from biological fluids. The number of circulating tumor DNA molecules with somatic mutations is very low compared to that of DNA molecules with wild type sequence and requires very sensitive methods for their detection. Here we discuss our efforts for developing such methods, studies for their validation, and their clinical applications.
9:00 cfDNA Ultra-Rare Allele Detection and Discovery
Seth Crosby, M.D., Director, Partnerships & Alliances, Washington University School of Medicine
9:25 Pharmacodynamic Assessment of Drug Response by Monitoring Mutational Load in Urinary Circulating Tumor DNA
Karena Kosco, Ph.D., Principal Scientist, Research and Development, Trovagene
The concept of liquid biopsies is expanding to include urine as a specimen type. Using Precision Cancer MonitoringSM (PCM) platform for quantitative ctDNA analysis at a single copy level, we demonstrate that drug-induced immediate early changes in ctDNA mutational load correlate with tumor burden and treatment response. As a non-invasive specimen, urine enables frequent monitoring of ctDNA, and this accessibility can be applied to investigating mechanisms of action of targeted therapeutics and, ultimately, cancer management.
9:55 Q&A with the Speakers
10:10 Coffee Break in the Exhibit Hall with Poster Viewing
10:40 Ultrasensitive Measurement of Circulating Tumor DNA to Assess Treatment Response and Resistance
Abhijit A. Patel, M.D., Ph.D., Assistant Professor, Therapeutic Radiology, Yale University School of Medicine
Our group has developed an ultrasensitive, multi-target assay that can identify and quantify mutant ctDNA using novel error-suppression techniques applied to next-generation sequencing data. Broad coverage of mutation hotspots and warm-spots allows detection of ctDNA without prior knowledge of the tumor’s mutation profile. Clinical examples will be presented in which this approach is used to noninvasively monitor changes in ctDNA levels in response to treatment and to track the emergence of mutations that confer resistance to targeted therapies.
11:05 Single-Tube Enrichment of Mutations in Cancer Gene Panels from Circulating DNA, Using COLD-PCR Prior to Targeted Amplicon Resequencing
G. Mike Makrigiorgos, Ph.D., Professor, Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School
Targeted re-sequencing of mutations in cancer-relevant genes provides opportunities for fine-tuning cancer therapy and follow-up during treatment, by examining mutations in tumors and bio-fluids. However, a major technical limitation has been the lack of sensitivity of cancer re-sequencing panels for mutations below 1-2% abundance, which is frequently the case for circulating DNA. We present a newly developed method via which mutations in numerous amplicons are first enriched via COLD-PCR in a single-tube reaction, prior to targeted re-sequencing. Using this approach, mutations of 0.01-0.1% abundance can be detected via next-generation sequencing.
11:30 Panel Discussion
Moderator: G. Mike Makrigiorgos, Ph.D., Harvard Medical School
12:00 pm Lunch on Your Own
1:30 Chairperson’s Remarks
Raghu Kalluri, M.D., Ph.D., Professor & Chair, Cancer Biology, MD Anderson Cancer Center
1:35 The Biology and Functional Contribution of Exosomes in Cancer Progression and Metastasis
Raghu Kalluri, M.D., Ph.D., Professor & Chair, Cancer Biology, MD Anderson Cancer Center
2:00 Characterization of Endothelial Microvesicles in Preclinical Species and Application to Drug Development
Sharon Sokolowski, MS, Senior Principal Scientist, Pfizer Global Research & Development
Microvesicles (0.5 – 1µM) in the peripheral blood of preclinical species have been evaluated as potential biomarkers of vascular perturbation or injury. Validation steps were completed to more fully characterize and understand the changes observed in peripheral blood microvesicle absolute counts in normal, dosed and diseased animals. While taking into consideration the advantages and caveats of microvesicle evaluation with current methods and instrumentation, application of microvesicles as safety and efficacy biomarkers during drug development was explored.
2:25 Extracellular Vesicles (EV) as a Molecular Diagnostic Platform
Clark Chen, M.D., Ph.D., Associate Professor and Chief, Stereotactic and Radiosurgery; Vice-Chairman, Academic Affairs, Neurosurgery, University of California, San Diego
Extracellular vesicles (EVs) are cell-secreted vesicles that range 30-2,000 nm in size. These vesicles are secreted by both normal and neoplastic cells. Physiologically, EVs serve multiple critical biologic functions, including cellular remodeling, intracellular communication, modulation of the tumor microenvironment, and regulation of immune function. Because EVs contain genetic and proteomic contents that reflect the cell of origin, it is possible to detect tumor-specific material in EVs secreted by cancer cells. Importantly, EVs secreted by cancer cells transgress anatomic compartments and can be detected in the blood, cerebrospinal fluid and other bio-fluids of cancer patients. In this context, there is a growing interest in analyzing EVs from the bio-fluid of cancer patients as a means of disease diagnosis and therapeutic monitoring. This talk will focus on the development of EVs as a diagnostic platform for the most common form of brain cancer, glioblastoma, and discuss potential clinical translational opportunities.
2:50 Novel Role of Microvesicles in Cardiovascular Diseases
Ming-Lin Liu, M.D., Ph.D., Research Assistant Professor, Dermatology, Perelman School of Medicine, University of Pennsylvania
3:20 Refreshment Break in the Exhibit Hall with Poster Viewing
4:10 Translational Circulating Biomarker Research for Drug Development
Yoshiya Oda, Ph.D., President, Biomarkers and Personalized Medicine Core Function Unit, Eisai
Biomarkers can play very important roles for drug development because biomarkers can show the data for target engagement, target modulation, patient stratification and drug efficacy. As a sample source of biomarkers, tissue is an issue, because the amount of tissue is very limited and it is hard to obtain biopsy samples in certain disease areas. Circulating biomarkers in serum/plasma are very practical and patient-friendly. Several real examples about proteins, lipids and miRNAs as circulating biomarkers will be shown during the presentation.
4:35 Next Generation Sequencing of Circulating Tumor Cells from the CELLSEARCH® System
Charles Saginario, Scientist, CRS Labs, Janssen Diagnostics
5:05-6:00 Welcome Reception in the Exhibit Hall with Poster Viewing
Wednesday, May 6
8:00 am Morning Coffee
8:25 Chairperson’s Remarks
David T.W. Wong, D.M.D., DMSc, Felix & Mildred Yip Professor and Associate Dean of Research, UCLA School of Dentistry; Director, Center for Oral/Head & Neck Oncology Research
8:30 Application of miR-Based Biomarkers in Diagnosis and Management of Liver Injury in Human Subjects
Jiri Aubrecht, Pharm.D., Ph.D., Senior Director and Safety Biomarker Group Lead, Drug Safety Research & Development, Pfizer
8:55 3'UTR SNPs that are Targets for A-I RNA Editing Control IGF1R mRNA Expression Levels in High-Risk Neuroblastoma
Danika Johnston, Ph.D., Research Associate, The Children's Hospital of Philadelphia
9:20 Exploration of Circulating Non-Coding RNAs as Cancer Biomarkers
Hui Ling, M.D., Ph.D., Odyssey Fellow, Experimental Therapeutics, MD Anderson Cancer Center
9:50 Coffee Break in the Exhibit Hall with Poster Viewing
10:45 Salivary Extracellular Non-Coding RNA Biomarkers
David T.W. Wong, D.M.D., DMSc, Felix & Mildred Yip Professor and Associate Dean of Research, UCLA School of Dentistry; Director, Center for Oral/Head & Neck Oncology Research
Extracellular RNAs (exRNAs) in human bodily fluids are emerging as effective biomarkers for detection of diseases. Saliva, as the most accessible and non-invasive bodily fluid, has been shown to harbor exRNA biomarkers for human diseases including cancer. Using high-throughput RNA-Seq, we conducted an in-depth bioinformatic analysis of non-coding RNAs (ncRNAs) in human cell free saliva (CFS) of healthy subjects with a focus on microRNAs (miRNAs), piwi-interacting RNAs (piRNAs) and circular RNAs (circRNAs) reporting the unusual abundance of piRNA and the first demonstration of circRNA in a bodily fluid.
11:10 MicroRNAs in Mediating Tumor Angiogenesis, Drug Resistance and Autophagy Responses in Human Cancers
Bing-Hua Jiang, Ph.D., Professor, Pathology, Anatomy and Cell Biology, Thomas Jefferson University
Our recent study demonstrates that a number of microRNAs (miRNAs) are downregulated in several kinds of human cancers including ovarian, breast, lung, colon and glioma; and that levels of miRNA suppression are associated with cancer development and drug resistance. To understand the mechanism, we found that several different kinds of miRNAs are involved in tumor growth, angiogenesis, drug resistance and autophagy responses through HER2, EGFR, IGF-IR and ATG14 pathways. The miRNA suppression is regulated by DNA methylation and reactive oxygen species.
11:35 Liquid Biopsies to Monitor Disease Progression and Therapeutic Response in Cancer
Anton Wellstein, M.D., Ph.D., Professor, Oncology, Pharmacology and Medicine, Georgetown University Medical School; Associate Director, Basic Science, Lombardi Comprehensive Cancer Center
Clinically detectable cancer should be considered as a systemic disease. Cancer tissue analysis provides a snapshot of the makeup of the local disease and/or metastases that is limited by physical access to cancerous sites. In contrast, serial blood samples provide a source of biomarkers that can reveal real-time changes due to altered disease stage and/or treatment responses. The utility of circulating microRNAs will be discussed.
12:00 pm Close of Conference