Monday, March 7
10:30 am Conference Program Registration Open
11:50 Chairperson’s Opening Remarks
Klaus Pantel, M.D., Professor and Founding Director, Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf
12:00 pm Liquid Biopsy: Expectations and Required Steps to Bring It into Clinical Practice
Klaus Pantel, M.D., Professor and Founding Director, Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf
Circulating tumor cells (CTCs), nucleic acids (ctDNA, cfmiRNA) and exosomes in the blood of cancer patients have received increasing attention as new diagnostic tool enabling “liquid biopsies”. The perspective to avoid invasive tissue biopsies and obtain similar or even more information by a “simple” blood test has enormous implications in cancer diagnostics. Here the expectations and future steps required to bring liquid biopsies into clinical practice will be discussed.
12:30 Circulating Tumor Cells as a Biomarker of Treatment Efficacy and Prediction in Castration-Resistant Prostate Cancer
Howard I. Scher, M.D., Chief, Genitourinary Oncology Service; Member and Attending Physician, Department of Medicine, Memorial Sloan Kettering Cancer Center; Professor, Medicine, Weill Cornell Medical College
Pre and post-therapy circulating tumor number has been shown to be prognostic for survival. Use in clinical practice and in drug development as a measure of treatment efficacy has been more limited. Analyses of the strength of association of the enumeration biomarker with survival will be discussed along with a recent analysis showing that a CTC enumeration biomarker in combination with LDH was shown to meet the Prentice Criteria for individual-patient level surrogacy. Use of a predictive biomarker to guide treatment selection will also be discussed.
1:00 Session Break
1:15 Luncheon Presentation I: Size-Based Isolation of
Circulating Tumor Cells Associated to Droplet Digital PCR
Allow Prediction of KRAS Mutations in Patients with
Colorectal Cancer before Tumor Surgery
Jérôme A. Denis, M.D., Ph.D., Sorbonne Universités
1:45 Luncheon Presentation II: Comprehensive
Ultra-Sensitive CTC Analysis in the Management of Cancer
Veena Singh, M.D.,Senior Vice President & Senior Medical Director, Biocept, Inc.
Circulating tumor cells (CTCs) isolated solely by EPCAM capture and their CK positive, CD45 negative profile miss CK negative non-EPCAM expressing CTCs. These maybe cancer stem cells or those with epithelial mesenchymal transition, and possibly more clinically relevant. Hence we developed a multi-antibody approach for characterization of all CTC phenotypes.
2:15 Session Break
2:30 Chairperson’s Remarks
Robert Daber, Ph.D., Vice President, Genomics Operations and Development, Laboratory Medicine, Bio Reference Laboratories
2:40 Assessment of FFPE Samples for Success in NGS
Helen Fernandes, Ph.D., Director, Molecular Pathology, Pathology & Laboratory Medicine, Weill Cornell Medical College
This presentation will discuss several important issues, such as: RNA detection in cancer tissues stored in FFPE samples, profiling microRNA expression, FFPE DNA quality control and its correlation with NGS data, and understanding pre-analytic effects on RNA gene expression.
3:10 Quantitative Comparison of Biomarkers by IHC vs mRNA Using a Nearly Point of Care Cancer Biomarker Platform
David L. Rimm, M.D., Ph.D., Professor, Pathology, Executive Director, Translational Pathology, Director, Yale Pathology Tissue Services, Yale University
The measurement of tissue biomarkers is a challenge in the US, but much more so in less developed countries. Some drugs, like Tamoxifen are inexpensive and effective but need a companion diagnostic test. This work will describe the comparison of a low cost, mRNA based platform for measuring Estrogen Receptor and other tissue biomarkers with immunohistochemistry and quantitative immunofluorescence.
3:40 NGS Applications with FFPE Samples: No Longer a Pipedream
Andrew J. Hollinger, Application Scientist, Broad Genomics Platform, Broad Institute.
The Genomics Platform at the Broad Institute has initiated a number of projects to explore QC of FFPE samples upstream of NGS applications resulting in development of protocols and processes that provide insight into likelihood of success for various NGS processes. This has been enabled in large part by the vast number of samples and large collections of FFPE samples that have been processed to date. Here we discuss our approach to preserving usage of nucleic acid from these limited sample types, high-throughput processing, DNA and RNA QC metrics to estimate likelihood of success, and NGS metrics of interest when working with FFPE.
4:10 Standardizing Molecular Pathology with Fully
Automated DNA and RNA Extraction from Formalin-Fixed,
Paraffin-Embedded (FFPE) and Fresh Frozen (FF) Tissue
Guido Hennig, Ph.D., Senior Global Scientific Affairs Manager, BU Molecular Global Marketing, Siemens Healthcare Diagnostics
Molecular analysis in FFPE/FF tissue is important in retrospective biomarker studies, biobanking and molecular pathology. The discussed Siemens Tissue Preparation System (TPS) fully automates and standardizes extraction of high quality DNA and RNA from any tissue for PCR and sequencing applications.
4:25 Automating NGS Sample Prep for Challenging Samples and Niche Applications
Brian Idoni, Genomics Sales Specialist, Beckman Coulter Life Sciences
This presentation will discuss Biomek-Automated solutions for NGS sequencing applications including HLA, cfDNA from Plasma, exosomes and working with very low input samples.
4:40 Refreshment Break and Transition to Plenary Session
5:00 Plenary Keynote Session
6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing
7:30 Close of Day
Tuesday, March 8
7:00 am Registration Open and Morning Coffee
8:00 Plenary Keynote Session
9:00 Refreshment Break in the Exhibit Hall with Poster Viewing
10:05 Chairperson’s Remarks
David L. Rimm, M.D., Ph.D., Professor, Pathology, Yale University
10:15 Tissue-Based Assessment of PD-L1 and Other Tumor Microenvironmental Factors in Melanoma Specimens
Janis M. Taube, M.D., MSc, Director, Dermatopathology; Assistant Professor, Dermatology and Pathology, Johns Hopkins
Immunohistochemical detection of PD-L1 and other checkpoint molecules may serve as biomarkers for selecting immunotherapeutic regimens for patients with advanced melanoma. The evaluation of the utility of PD-L1 as a biomarker has been hampered by the different antibodies and assays used. We will discuss the current issues associated with immune checkpoint companion diagnostics and potential future applications for use of these assays in patients with melanoma.
10:45 Tissue-Based Analyses to Guide Immunotherapy for Lymphoma
Scott Rodig, M.D., Ph.D., Hematopathologist, Pathology, Brigham and Women’s Hospital
Targeted immunotherapy has achieved long-lasting clinical responses in a subset of patients with a variety of aggressive malignancies. I will discuss the cellular and molecular characteristics of classical Hodgkin lymphoma that render this tumor-type uniquely susceptible to PD-1 blockade and correlations between tissue-based biomarker analysis and clinical outcome with either conventional chemotherapy or immunotherapy, and extensions of these observations to additional lymphoma subtypes.
11:15 Immune Profiling of Lung Cancer Tissue Specimens
Ignasio I. Wistuba, M.D., Department Chair, Translational Molecular Pathology, Division of Pathology/Lab Medicine; Anderson Clinical Faculty Chair, Cancer Treatment and Research, The University of Texas MD Anderson Cancer Center
The anti-tumor benefit of blocking immune checkpoints in lung cancer, particularly PD-1 and PD-L1, has revolutionized the therapy of this disease. Because of variable responses to immunotherapy (IMT), there is an urgent need for predictive biomarkers to guide personalization of lung cancer treatment. A comprehensive approach to identify and validate IMT-related biomarkers in lung cancer tissue specimens, including digital pathology and genomic methodologies, will be described.
11:45 Beyond PD-L1: Other Potential Companion Diagnostic Tests for Immune Checkpoint Therapy
David L. Rimm, M.D., Ph.D., Professor, Pathology, Yale University
The current companion diagnostic tests and nearly all publications related to immune checkpoint therapies are based on assessment of PD-L1. Some assess PD-L1 in the epithelial component while others emphasize stromal expression. However, there may be other methods for assessment of response to these therapies based on the presence of subsets of T-cells or assessment of the activation of these T-cells. It is also possible that assessment of other co-stimulators or competitive receptors may influence prediction of response to therapy. These non-Pd-L1 methods will be reviewed in this lecture.
12:15 pm Session Break
12:25 Luncheon Presentation I: Shared Accountability: How Genomics & Informatics Will Engage Consumers, Providers and Payers toward true Personalized Medicine
Satnam Alag, Ph.D., Vice President, Software Development, Enterprise Informatics
Genomics data is a big deal when context and meaning is attached to it. Smart data - the right data at the right time to the right person - can help Consumers, Providers and Payers enhance and inform care decisions. That's the prize but how do you get your hands on it? We will focus on Genomics & Informatics and how companies like Illumina are working to provide solutions.
12:55 Luncheon Presentation II: Integrated Oncology Diagnostics enabled by Digital Pathology
Reinhold Wimberger-Friedl phd principal scientist, Philips Research Europe Philips
At Philips we develop an integrated approach of staining-based and molecular characterization of the tumor and its micro-environment. Digital pathology with WSI analytics enables a comprehensive quantification of cellular composition of the tumor. A proprietary model determines the tumor-driving signaling pathways from mRNA expression profiles.
1:25 Refreshment Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Steven A. Soper, Ph.D., Professor, Biomedical Engineering & Chemistry; Associate Editor, Analyst; Director, Center for BioModular Multiscale Systems, University of North Carolina
2:10 Circulating Tumor Cells and Mouse Models of Serous Ovarian Cancer
Victoria Bae-Jump, M.D., Ph.D., Associate Professor, Division of Gynecologic Oncology, University of North Carolina
Ovarian cancer (OC) screening is considered the “holy grail” of gynecologic oncology, given that attempts using CA-125 and other tumor markers as well as ultrasound imaging have largely been unsuccessful in screening for this disease. Our novel circulating tumor cell assay employs a dual selection strategy and is being explored using a genetically engineered mouse model (K18-gT121+/-;p53fl/fl;Brca1fl/fl) of OC, providing access to well-defined early and late stage disease blood samples.
2:40 Orthotopic Mouse Models of Cancer and GFP Labeling for the Study of Circulating Tumor Cells
Robert M. Hoffman, Ph.D., President, AntiCancer, Inc.; Professor, Surgery, University of California, San Diego
We have previously determined that orthotopic mouse models of cancer produce viable circulating tumor cells (CTCs) in contrast to ectopic models. We have also demonstrated that green fluorescent protein (GFP) labels CTCs for further analysis such as metastatic potential or chemosensitivity testing. Patient CTCs can also be selectively labeled with GFP ex vivo for analysis.
3:10 Early Pancreatic Markers, Biomarkers for Exosome Isolation
Raghu Kalluri, M.D., Ph.D., Professor & Chair, Cancer Biology, University of Texas MD Anderson Cancer Center
Exosomes are lipid-bilayer-enclosed extracellular vesicles that contain proteins and nucleic acids. They are secreted by all cells and circulate in the blood. Specific detection and isolation of cancer-cell-derived exosomes in the circulation is currently lacking. Using mass spectrometry analyses, we identify a cell surface proteoglycan, glypican-1 (GPC1), specifically enriched on cancer-cell-derived exosomes.
3:40 Liquid Biopsy Using Exosome RNA and ctDNA, Realizing the “Holy Grail” of Personalized Medicine
Johan Skog, Ph.D., CSO, Research & Development, Exosome Diagnostics
Recently, ctDNA has shown promise for cancer mutation detection. ExoDx platform of exoRNA + ctDNA addresses the limitations of ctDNA alone. ExoRNA is abundant from bio-fluids and yields mutations, splice variants, and fusions.
4:10 St. Patrick’s Day Celebration in the Exhibit Hall with Poster Viewing
5:00 Breakout Discussions in the Exhibit Hall
These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion
Patient-Derived Orthotopic Xenografts
Robert M. Hoffman, Ph.D., President, AntiCancer, Inc.; Professor, Surgery, University of California, San Diego
- Patient-derived orthotopic xenografts (PDOX) models
- Better mimic of metastasis than subcutaneous xenografts
- Orthotopic tumor mouse models can replicate patient tumor behavior
- Subcutaneous tumor mouse models do not replicate patient tumor behavior
- Patient-derived orthotopic xenograft models have important potential for individualized cancer therapy
Challenges and Opportunities for Therapeutically Targeting Cells in Blood
Michael R. King, Ph.D., Daljit S. and Elaine Sarkaria Professor of Biomedical Engineering, Meinig School of Biomedical Engineering, Cornell University
- Unique aspects of the vascular microenvironment (shear stress, blood cells and plasma)
- The “best” and most relevant animal models of metastatic cancer
- Clinical translation and next steps
6:00 Close of Day
Wednesday, March 9
7:00 am Registration Open
7:00 Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee
8:00 Plenary Keynote Session Panel
10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall
10:50 Chairperson’s Remarks
Steven A. Soper, Ph.D., Professor, Biomedical Engineering & Chemistry; Associate Editor, Analyst; Director, Center for BioModular Multiscale Systems, University of North Carolina
11:00 KEYNOTE PRESENTATION: New Tools for the Isolation of Circulating Markers: Integrated Microfluidic Systems for the Efficient Isolation of CTCs, Cell-Free DNA and Exosomes
Steven A. Soper, Ph.D., Professor, Biomedical Engineering & Chemistry; Associate Editor,
Analyst; Director, Center for BioModular Multiscale Systems, University of North Carolina
Liquid biopsies are generating interest within the biomedical community due to
the simplicity for securing important markers to realize precision medicine. These
circulating markers consist of whole cells such as CTCs, molecules such as cell-free
DNA and nanovesicles such as exosomes. We are developing a microfluidic system
that can process whole blood and select all three of these markers from a single
blood sample.
11:30 Why Do Cancer Cells Move?
Daniel Irimia, M.D., Ph.D., Assistant Professor, Division of Surgery, Science & Bioengineering, Massachusetts General Hospital and Harvard Medical School; Associate Director, BioMEMS Resource Center
When cancer cells leave the tumor, they set in motion a cascade of events that ends with the formation of distant metastases and the death of 90% of cancer patients. However, despite their importance, our understanding of the conditions that trigger cancer cell migration is very limited. In this presentation, I will discuss the design of novel microfluidic tools which revealed the unexpected ability of cancer cells to navigate microscopic mazes along the shortest path and helped identify novel mechanisms for the cancer cell migration.
12:00 pm Extracellular Vesicles as Couriers of Cancer Information
Hakho Lee, Ph.D., Assistant Professor, Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School
Tumor cells release a variety of extracellular vesicles (EVs) which carry information in the form of protein, DNA and RNA. For example, microRNAs can be transferred via EVs to normal cells, thereby changing their phenotype in support of tumor progression. These vesicles and other extracellular RNA vehicles also carry a representation of the transcriptome of the tumor cells which can be found in biofluids and reports on the genetic drivers and status of the cancer.
12:30 Session Break
12:40 Luncheon Presentation: Telomerase-directed tagging of Circulating Tumor Cells
Jay F. Dorsey, M.D., Ph.D., Assistant Professor, Department of Radiation Oncology, University of Pennsylvania
In this presentation we will discuss the association of “telomerase-dependent CTC findings” with treatment response in a variety of cancer patient populations including malignant glioma and non-small cell lung cancer (NSCLC) along with an analysis of molecular driver characterization in CTCs.
1:10 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing
1:50 Chairperson’s Remarks
Kai Wang, Ph.D., Principal Scientist, Institute for Systems Biology
2:00 Tethered Lipoplex Nanoparticle (TLN) Biochips For Extracellular Vesicles Based Early Disease Diagnosis and Prognosis
L. James Lee, Ph.D., Helen C. Kurtz Chair, Chemical & Biomolecular Engineering, Ohio State University
Circulating extracellular vesicles (EVs) is currently the major focus of non-invasive early disease detection and prognosis. We show that biochips using tethered lipoplex nanoparticles (TLNs) containing molecular beacons can capture cell-derived EVs from body fluids, and identify encapsulated microRNAs/mRNAs and EV surface membrane protein targets with very small sample size (~20 uL blood for 2 targets) and higher sensitivity than qRT-PCR. We will present TLN applications to cancer and non-cancer diseases.
2:30 The Complexity, Function and Applications of RNA in Circulation.
David Galas, Ph.D., Principal Scientist, The Pacific Northwest Diabetes Research Institute
MicroRNAs (miRNAs) have been implicated to play key roles in normal physiological functions, and altered expression of specific miRNAs has been associated with a number of diseases. It is of great interest to understand their roles and a prerequisite for such study is the ability to comprehensively and accurately assess the levels of the entire repertoire of miRNAs in a given sample. It has been shown that some miRNAs frequently have sequence variations termed isomirs.
3:00 Best Practices for Fusion Detection by Targeted RNA Sequencing: Pre-Analytical Considerations, Assay Validation and More
Robert D. Daber, Ph.D., Director, Research and Development and Sequencing Operations, Bio-Reference Laboratories
This presentation will discuss challenges and benefits of NGS based targeted RNA sequencing in the detection of gene fusion events, including, nucleic acid isolation, sample preparation and downstream data processing. There are a number of specific challenges related to RNA sequencing, standardized quality control metrics both before and after library prep are clearly needed.
3:30 Sponsored Presentation (Opportunity Available)
4:00 Session Break
4:10 Chairperson’s Remarks
Stuart S. Martin, Ph.D., Associate Professor, Physiology, Greenebaum NCI Cancer Center, University of Maryland School of Medicine
4:15 Small Cell Lung Cancer Circulating Tumour Cell-Derived Explants – A New Preclinical Platform for Examining Drug Response
Kristopher Frese, Ph.D., Postdoctoral Fellow, University of Manchester
Due in part to the paucity of tissue samples available for preclinical studies, the past 30 years of research have not provided any new therapeutic options for small cell lung cancer (SCLC). We have recently demonstrated that SCLC circulating tumour cells (CTCs) are tumorigenic in mice and the resulting patient CTC-derived explants (CDX) mirror patients’ disease both in vivo and in vitro. Studies examining the therapeutic efficacy of novel targeted agents are currently underway.
4:45 Antibody-Free Capture of Tumor Cells from Blood and Novel CTC-Targeting Therapeutics
Michael R. King, Ph.D., Daljit S. and Elaine Sarkaria Professor of Biomedical Engineering, Meinig School of Biomedical Engineering, Cornell University
Our laboratory uses surfactant-nanotube complexes to enhance E-selectin-mediated capture and isolation of tumor cells without the use of capture antibodies. Functionalization with sodium dodecanoate surfactant induces a switch to firm cellular adhesion of tumor cells with a simultaneous de-adhesion of blood leukocytes. This system has proved valuable in testing new liposome-based therapeutics designed to target tumor cells in blood for the prevention of metastasis.
5:15 POSTER 99: Microfluidic Isolation of Circulating Tumor Cells from Different Venous Sources in Early Lung Cancer
Vasudha Murlidhar, Ph.D., Candidate, Nagrath Lab, Department of Chemical Engineering, University of Michigan, Ann Arbor
5:45 Close of Conference Program