07:45 | Conference Registration, Conference Materials Pick-Up, Morning Coffee and Breakfast Pastries in the Exhibit Hall |
| Session Title: Emerging Trends in Liquid Biopsies for Cancer |
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08:30 | | Keynote Presentation Liquid Biopsy Tests Move Towards Routine Patient Care and Management Walter Koch, Vice President, Roche Molecular Systems, United States of America
Over the past decade several tissue-based companion diagnostic assays have gained FDA approval in conjunction with targeted cancer therapies, resulting in improved treatment options for many cancer patients. Despite various international guidelines, not all patients are tested, due in part to limited tissue availability, or health status limits on acquiring a re-biopsy sample. This has spurred development of so-called liquid biopsy tests which use body fluids such as plasma to ascertain tumor mutational status in circulating cell free DNA originating from tumors, or circulating tumor cells. On June 1, 2016 the FDA-approved the cobas® EGFR Mutation Test v2 real-time PCR test for the qualitative detection of defined mutations of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer (NSCLC) patients. For the first time the test can be used with both formalin-fixed paraffin-embedded tumor tissue (FFPET) as well as circulating-free tumor DNA (cfDNA) from plasma derived from EDTA anti-coagulated peripheral whole blood. The test is indicated as a companion diagnostic to aid in selecting NSCLC patients for treatment with the targeted therapies including TARCEVA®. This milestone heralds the first of many to come that will provide additional opportunities for cancer patients to be evaluated with blood samples for treatment with targeted therapies. Analogous to HIV viral load testing, further clinical development will likely extend the use of such blood tests to allow monitoring of initial drug response as well as disease progression and/or development of specific resistance mutations. Collectively these advances promise to provide important clinical information not easily obtained by repeat tissue biopsy approaches. |
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09:00 | | Keynote Presentation Promise of Circulating Tumor Cell and Cell-Free DNA Assays in the Oncology Clinic Minetta Liu, Associate Professor and Chair, Oncology Research, Mayo Clinic, United States of America
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09:30 | | Keynote Presentation Cell Free DNA, RNA and Exosome Liquid Biopsy Cancer Diagnostics Michael Heller, Professor, Dept Bioengineering, University of California-San Diego, United States of America
Circulating cell free (ccf) DNA, RNA and exosomes are now considered important biomarkers for liquid biopsy cancer diagnostics, and also hold great promise for early cancer detection. Nevertheless, the isolation of these biomarkers from patient samples requires relatively complex, time consuming and expensive procedures which greatly limits their practical use for most cancer diagnostic applications. New AC dielectrophoretic (DEP) microarray/chip devices now allow 15-20-minute isolation of cancer related ccf-DNA, RNA and exosome biomarkers from 20-50ul of blood, plasma or serum. After isolation of the biomarkers, specific fluorescent dyes can be used first to simultaneously detect the different biomarker levels directly on the chip (in-situ). In a subsequent step, immunofluorescent analysis can be carried out to identify specific protein biomarkers on the exosomes. Finally, the ccf-DNA and RNA (mRNAs and miRNAs release from the exosomes) can be eluted from the DEP chip, and PCR and sequencing analysis carried out to identify the cancer-related point mutations and other polymorphisms, as well as to further verify the tissue origin of the biomarkers. In the case of our Chronic Lymphocytic Leukemia clinical studies, final PCR and DNA sequencing results for the CLL related ccf-DNA isolated by DEP were found to be exactly comparable to two much more complex and time consuming “gold standard” procedures. In the case of glioblastoma exosomes isolated from plasma, exosome-specific surface and interior proteins CD63 and TSG101 could be detected by immunofluorescence, and mutated EGFRvlll mRNA was detected by RT-PCR. Finally, the exosomal related protein biomarker Glypican-1 could be isolated from pancreatic cancer patient plasma samples by DEP and detected on-chip by immunofluorescence. Thus, DEP represents a powerful new minimally invasive technology for cancer diagnostics that is particularly well suited for the rapid isolation of cell free nucleic acid and exosomes.
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10:00 | | Keynote Presentation Diagnosis of Ischemic Heart Disease Using Plasma Extracellular Vesicle Sub-fractions Dominique PV de Kleijn, Professor Experimental Vascular Surgery, Professor Netherlands Heart Institute, University Medical Center Utrecht, The Netherlands, Netherlands
Cardiovascular Disease (CVD) is with the cardiovascular events of Ischemic Heart Disease and Stroke, the number 1 and 2 cause of death in the world and expect to increase especially in Asia. Ischemic heart disease (IHD) comprises 3 entities: stable coronary artery disease (SCAD), unstable angina (UA) and myocardial infarction (MI). Because IHD is associated with an increased risk of adverse clinical events such as heart failure and death, early recognition of IHD is of utmost importance. However, to diagnose IHD is challenging, as many patients present with atypical symptoms. It is known that women have a different symptom sensation than men. Troponins are the main diagnostic tool for detection of MI. Blood biomarkers for SCAD (typically causing stable angina) and UA, however, are not available. These diagnoses frequently require hospital visits/admissions for time-consuming and costly (non)invasive tests. Using 4 plasma fractions, we show that the plasma extracellular vesicle content in these 4 fractions can be used as an accurate source for early diagnosis of SCAD and UA. |
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10:30 | Coffee Break and Networking in the Exhibit Hall: Visit Exhibitors and Poster Viewing |
11:00 | NGS Libraries From Cell-free DNA Containing Molecular Tags Prepared with ThruPLEX® Technology Improve Ability to Detect Rare Alleles Karl Hecker, Vice President of Product Development, Rubicon Genomics, Inc., United States of America
Next Generation Sequencing (NGS) of cell-free DNA (cfDNA) enables non-invasive access to genetic information from liquid biopsies. Key to identifying rare genetic mutations is improved sequencing accuracy and the ability to distinguish between biological and PCR duplicates. Rubicon Genomics’ ThruPLEX Plasma-seq was developed specifically for cell-free DNA. |
11:30 | Combining CTC and ctDNA Platforms from the Same Clinical Samples to Expand Liquid Biopsy Biomarker Content Lyle Arnold, Chief Scientific Officer, Biocept, United States of America
Liquid biopsies offer the opportunity to interrogate a number of different target sample types, including ctDNA and CTCs. At Biocept both ctDNA and CTCs are used for identifying medically actionable biomarkers. The combination of these technologies has enabled the clinical validation of an array of biomarkers from single blood samples. These include mutational analysis for EGFR, KRAS, and BRAF, as well as FISH and protein analysis for HER2, FGFR1, MET, ALK, ROS1, ER, PR, AR and PDL-1 across a range of cancer types. In addition, CTCs can be isolated from the microchannel and interrogated using other means, including NGS. |
12:00 | Technology Spotlight: truXTRAC cfDNA: The High Throughput, High Yield Adaptive Focused Acoustics™ (AFA)-Mediated Circulating Cell-Free DNA Extraction and Purification System Hamid Khoja, Principal Scientist, Covaris, Inc.
The presentation will provide data illustrating the effects of an active extraction method of ccfDNA from plasma, and comparison data with the currently-used protocols. |
12:30 | Networking Lunch in the Exhibit Hall: Visit Exhibitors and Poster Viewing |
| Session Title: Analyte Classes for Liquid Biopsy Development -- Cell-free DNA (cfDNA), Circulating Tumor Cells (CTCs) and Extracellular Vesicles (EVs) |
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13:30 | Longitudinal Whole Exome Investigation of Mutational Heterogeneity in Single CTCs in a Patient with Triple-Negative Breast Cancer Eric Kaldjian, Chief Medical Officer, RareCyte, United States of America
We performed whole exome sequencing of single CTCs from a patient with metastatic triple-negative breast cancer to investigate the evolution of genetic heterogeneity during therapy. CTCs were identified using the AccuCyte-CyteFinder system (RareCyte) and individually retrieved from microscope slides using the integrated CytePicker function. Single cell whole genome amplication was performed followed by whole exome sequencing. Computational biology tools were employed to analyze genomic DNA sequence from multiple CTCs, white blood cells and ctDNA from various time points. Genomic sequence alterations were observed to evolve over the course of therapy in individual CTCs. These alterations appear to be generally consistent within CTC at a given time point. The number of predicted deleterious and cancer driver mutations per CTC were observed to increase in frequency after effective treatments, suggesting that the number of such alterations may be associated with resistance to therapy. |
14:00 | | Keynote Presentation Digital Quantification of Biomarkers in Liquid Biopsies Using the Integrated Comprehensive Droplet Digital Detection (IC 3D) System Weian Zhao, Associate Professor, Department of Biomedical Engineering, University of California-Irvine, United States of America
We will present a new platform technology that could detect rare blood biomarkers including infections, CTCs, miRNA and exosomes with extremely high sensitivity, specificity, throughput and minimal sample processing. |
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14:30 | Technology Spotlight: Advances in Microscopy-Based Single Cell Isolation Chris Wetzel, Director of Sales and Marketing, MMI Microscope-based Single Cell Isolation
The isolation of single cells can often present challenges depending on the properties of the cells and the surrounding medium. This presentation deals with state-of-the-art techniques how to isolate cells from tissue (Laser Micro Dissection) and liquid suspensions (automated Micro Capillary) including live cells and adherent cells. |
15:00 | | Keynote Presentation Circulating Tumor DNA in Advanced-Stage Cancer Patients – Somatic Genomic Landscape and its Clinical Utility AmirAli Talasaz, Co-Founder, President & COO, Guardant Health, United States of America
Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) enables non-invasive profiling of solid tumor cancers. Liquid biopsy studies to date have been limited to modest-size cohorts and case studies. Somatic genomic profiles of over 15,000 patients with advanced-stage clinical cancer were determined by a highly accurate, deep-coverage ctDNA NGS test targeting 70 genes (Guardant360). Frequencies of somatic ctDNA alterations per gene were compared to those previously described in tissue sequencing projects (e.g., TCGA). Accuracy of ctDNA sequencing (PPV) was assessed by comparing with matched tissue tests. Different classes of clinical outcome benefits have been observed by liquid biopsy by detecting actionable mutations in cases with tissue QNS or actionable mutations emerging at time of progression or under-genotyped tumors. |
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15:30 | Coffee Break and Networking in the Exhibit Hall: Visit Exhibitors and Poster Viewing |
16:00 | Circulating Vesicles at the Nanoscale Shivani Sharma, Associate Director, California NanoSystems Institute, California NanoSystems Institute, UCLA, United States of America
The role of nanotechnology in understanding the nanoscale structure, mechanics and biomolecular characteristics of circulating extracellular vesicles (EVs) will be discussed. |
16:30 | | Keynote Presentation Integrated Microfluidic Systems for the Isolation of CTCs, cfDNA and Exosomes Steve Soper, Foundation Distinguished Professor, Director, Center of BioModular Multi-Scale System for Precision Medicine, The University of Kansas, United States of America
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17:00 | | Keynote Presentation Could Precision Medicine be Tailor-Made for Metastatic Head and Neck Cancers Chamindie Punyadeera, Associate Professor, Institute of Health and Biomedical Innovation, Queensland University of Technology, Australia
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17:30 | | Keynote Presentation Profile CTC Stiffness by Mechanical Separation Chips to Better Predict Breast Cancer Metastasis Lidong Qin, Professor and CPRIT Scholar, Houston Methodist Research Institute, United States of America
Detection of Circulating Tumor Cells (CTCs) has emerged as a promising minimally invasive prognostic tool to stage cancer metastasis; however, the identification and characterization of CTCs require extremely sensitive and specialized analytical methods, as CTCs are rare, heterogeneous, and associated with a complexity of blood sample matrix. To combat the current CTC detection limitations, we plan to incorporate the filtration method based on a size exclusion capability of microfluidics chips with cocktails of biomarker-specific antibodies to stain and image CTCs. By observing the cell distribution on the chip based on CTCs’ capability in crossing micro-barrier arrays, we can profile the captured CTCs’ stiffness and correlate it to the cancer metastasis potential. We expect to provide a better cancer prognosis tool than counting cells. |
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18:00 | | Keynote Presentation Clinical Applications of NanoVelcro Rare-Cell Assays for Detection and Characterization of Circulating Tumor Cells Hsian-Rong Tseng, Professor, Crump Institute for Molecular Imaging, California NanoSystems Institute, University of California-Los Angeles, United States of America
Circulating tumor cell (CTC) is regarded as a liquid biopsy of tumor, allowing non-invasive, repetitive, and systemic sampling of disease. Although detecting and enumerating CTCs is of prognostic significance in metastatic cancer, it is conceivable that performing molecular and functional characterization on CTCs will reveal unprecedented insight into the pathogenic mechanisms driving lethal disease. Nanomaterial-embedded cancer diagnostic platforms, i.e., NanoVelcro CTC Assays represent a unique rare-cell sorting method that enables detection isolation, and characterization of CTCs in peripheral blood, providing an opportunity to noninvasively monitor disease progression in individual cancer patients. Over the past decade, a series of NanoVelcro CTC Assays has been demonstrated for exploring the full potential of CTCs as a clinical biomarker, including CTC enumeration, phenotyping, genotyping and expression profiling. In this presentation, Dr. Tseng will briefly introduce the development of three generations of NanoVelcro CTC Assays, and highlight the clinical applications of each generation for various types of solid cancers, including prostate cancer, pancreatic cancer, lung cancer, kidney cancer, liver cancer, and melanoma. |
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18:30 | Cocktail Reception for All Conference Attendees: Enjoy Beer, Wine, Appetizers and Network with Fellow Delegates, Speakers, Exhibitors Pool-Side |
20:00 | Close of Day 1 of the Conference. Continue Networking in Downtown San Diego (Trolleys to the City are Available Right Behind the Conference Venue). |