The way we think about cancer is about to change. What we used to treat as a random occurrence is becoming both predictable and preventable through an array of emerging circular biomarkers. Through the use of circulating tumor cells, cell-free circulating
DNA, exosomes, exomers, oncosomes and other extracellular vesicles, we are now able to understand early stages of cancer and apply molecular profiling to clinical trial selection, patient treatment and minimal residual disease detection. The applications
are expanding outside of cancer to include transplant medicine, cardiovascular disease, CNS, autoimmune and infectious disease. Encounter the latest research results and clinical trial data while networking with leaders in the field.
Final Agenda
Scientific Advisory Board
Stefanie Jeffrey, MD, John and Marva Warnock Professor, Surgery; Chief, Surgical Oncology Research, Stanford University School of Medicine
Stuart S. Martin, PhD, Professor, Physiology, Marlene and Stewart Greenebaum NCI Comprehensive Cancer Center, University of Maryland School of Medicine
Catherine Alix-Panabières, PhD, Director, Laboratory of Rare Human Circulating Cells (LCCRH), Pathology and Onco-Biology Department, University Medical Center of Montpellier
Klaus Pantel, MD, Professor and Founding Director, Institute of Tumor Biology, University, Medical Center Hamburg-Eppendorf
Steven A. Soper, PhD, Professor, Micro and Nanofabricated Tools for Biological Discovery and Medical Diagnostics, University of Kansas
Shannon L. Stott, PhD, Assistant Professor, Department of Medicine, Massachusetts General Hospital, Harvard Medical School; BioMEMS Resource Center, The MGH Cancer Center
Monday, March 11
10:30 am Conference Program Registration Open (South Lobby)
11:50 Chairperson’s Opening Remarks
Klaus Pantel, MD, Professor and Founding Director, Institute of Tumor Biology, University, Medical Center
Hamburg-Eppendorf
12:00 pm Circulating Tumor Cells in Breast Cancers: Current Clinical Validity and Utility
François-Clément Bidard, MD, PhD, Professor of Medical Oncology,
Institut Curie & Versailles St. Quentin University
Numerous clinical data have been collected regarding the clinical validity of CTC count and characterization in both early and advanced breast cancer patients. After having reviewed these data, we will discuss how CTC detection may help customize breast
cancer therapy.
12:20 Critical Assessment of the Challenges of Using Blood-Based Biomarkers in Prostate Cancer from a Clinical Point of View
Daniel C. Danila, MD, Medical Oncology Assistant Attending, Genitourinary Oncology Service, Department
of Medicine, Memorial Sloan Kettering Cancer Center
In addition to determining whether circulating tumor cells (CTC) can be used as prognostic biomarkers for patients needing further therapy, current studies have proposed many predictive and pharmacodynamic biomarkers to facilitate the doctor’s ability
to optimize and adjust dosage based on their ability to target specific pathways. Significant efforts have been focused on developing and analytically validating predictive biomarkers to select patients most likely to benefit the specific therapy.
12:40 Panel Discussion
1:00 Session Break
1:10 Luncheon Presentation I: Routine Capture and Analysis
of Rare Cells for Non-Invasive Diagnostics
Paul Smith, CEO, ANGLE
Biosciences Inc.
This session will focus on key challenges with the capture and analysis of CTCs and CTC clusters for liquid biopsies. Potential applications utilizing epitope independent capture coupled with imaging and highly sensitive, multiplexed molecular techniques
will be presented.
1:40 Luncheon Presentation II: Introducing Circulating Stromal Cells and their Clinical Applications
Daniel Adams, Senior Research Scientist, Creatv MicroTech Inc
CellSieveTM microfiltration efficiently collects Circulating Stromal Cells (CStCs) along with CTCs from cancer patient blood. Clinical utility of CStCs includes early detection, companion diagnostics, monitoring treatment response,
prognosis and pathogenesis – redefining cancer screening and diagnostics.
2:10 Session Break
2:30 Chairperson’s Remarks
Klaus Pantel, MD, Professor and Founding Director, Institute of Tumor Biology, University, Medical Center
Hamburg-Eppendorf
2:40 The Whole Transcriptional Landscape of Circulating Tumors Cells in Metastatic Breast Cancer
Julie E. Lang, MD,
Associate Professor of Clinical Surgery; Director, Breast Cancer Program, Department of Surgery, Keck School of Medicine, University of Southern California
The aim of our study was to evaluate if RNA Seq of circulating tumor cells could serve as a surrogate for biopses of macrometastases. We evaluated treatment opportunities based on circulating tumor cell profiles and tracked them under the selection
pressure of systemic therapy in Stage IV breast cancer. RNA Seq of circulating tumor cells may be used to discover molecular alterations that are potentially clinically actionable.
3:10 Large Oncosomes as a Source of Cancer-Specific Circulating Biomarkers
Dolores Di Vizio, MD, PhD, Division of Cancer Biology and Therapeutics, Departments
of Surgery, Biomedical Sciences and Pathology and Laboratory Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center
Extracellular vesicles (EVs) are heterogeneous membrane enclosed structures harboring molecular cargo from the cell of origin. Large oncosomes are a novel subtype of EV that is released by highly migratory cancer cells. Large oncosomes contain abundant
tumor-derived cargo, which can be analyzed upon purification from plasma and other biological fluids. Here we show analyses of protein, RNA and DNA in controlled system and patient plasma.
3:40 Molecular Analysis of Circulating Tumor Cells, Extracellular Vesicles and Nucleic Acids as Liquid Biopsy in the Follow-Up of Metastatic Breast Cancer Patients to Stratify Patients for Targeted Therapy
Prof. Dr. Sabine Kasimir-Bauer,
Head of Research Laboratory, Department of Gynecology and Obstetrics, University Hospital Essen
The so-called liquid biopsy is discussed to be a surrogate marker for therapy stratification of metastatic breast cancer patients. We compared and analyzed RNA profiles enclosed in circulating tumor cells or extracellular vesicles and performed mutational
analysis of cell-free DNA (cfDNA) in plasma samples (Next Generation Sequencing) in the follow-up of the disease to get insights into their feasibility for therapy stratification and to predict therapeutic options.
4:10 An Open, End to End, and Flexible Platform for Scalable CTC Collection, Identification, and Analysis
Tad George, PhD, Senior Director of Platform, Applications, RareCyte
RareCyte provides instrumentation and consumables that enable an exquisitely sensitive, accurate, simple, and repeatable workflow from liquid biopsy to single cell isolation. The open and end to end RareCyte CTC workflow will be the focus of this
talk.
4:40 Refreshment Break and Transition to Plenary Session
5:00 Plenary Keynote Session (Room Location: 3 & 7)
6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing
7:30 Close of Day
Day 1 | Day 2 | Day 3 | Download Brochure
Tuesday, March 12
7:30 am Registration Open and Morning Coffee (South Lobby)
8:00 Plenary Keynote Session (Room Location: 3 & 7)
9:15 Refreshment Break in the Exhibit Hall with Poster Viewing
10:15 Chairperson’s Remarks
Stuart S. Martin, PhD, Professor, Physiology, Marlene and Stewart Greenebaum NCI Comprehensive Cancer Center, University of Maryland School of Medicine
10:25 Chemotherapy-Induced Pro-Metastatic Changes in Breast Cancer Microenvironment
Maja H. Oktay, MD, PhD, Professor of Pathology, The L.G. Koss Division of Cytology, Montefiore Medical Center; Professor of Anatomy and Structural Biology; Director, Clinical Imaging Applications, Integrated Imaging
Program, Michael F. Price Center for Genetic and Translational Medicine, Albert Einstein College of Medicine
Chemotherapy may induce pro-metastatic changes within breast cancer microenvironment in both mouse and human breast cancer and subsequent hematogenous cancer cell dissemination to distant sites. Cellular and molecular mechanism involved in
chemotherapy-mediated cancer cell dissemination as well as pharmacological inhibitors of this process will be discussed.
10:55 RNA Signatures in CTCs for Precision Cancer Medicine
David T. Miyamoto, MD, PhD, Assistant Professor,
Radiation Oncology, Harvard Medical School; Department of Radiation Oncology, Center for Cancer Research, Massachusetts General Hospital
CTC analysis is a type of liquid biopsy that enables RNA expression profiling, an analysis not possible with ctDNA. Microfluidic enrichment of CTCs followed by RNA-based digital PCR enables the high-throughput and highly specific detection
of CTC molecular signatures in several cancers. These CTC signatures can predict therapeutic responses and may enable the early detection of invasive cancers, thus guiding the precision management of cancer patients.
11:25 Assessing PD-L1 Expression on CTCs and Correlation with Immunotherapy Response
Rajan Kulkarni, MD, PhD, Assistant Professor, Dermatology and CEDAR/Knight Cancer Institute, Oregon Health and Science University
PD-1 inhibitors have promising efficacy in several cancers. Circulating tumor cell (CTC) PD-L1 levels could supplement tissue PD-L1 biopsy results by sampling from disseminated tumor sites. Towards establishing CTCs as a screening tool, we
developed a protocol to isolate CTCs at high purity and immunostain for PD-L1. Monitoring of PD-L1 expression on CTCs could be an additional biomarker that may help in determining response to immunotherapies.
11:55 Molecular Heterogeneity as Expressed in Cells from Liquid Biopsies using CellSearch and DepArray in Multiple Myeloma
Steven
Gross, PhD, Head, CellSearch Assay Development, Research & Development, Menarini Silicon Biosystems Inc
Exploring the molecular heterogeneity as expressed in cells using CellSearch and DepArray technologies in multiple myeloma and other cancers.
12:25 Session Break
12:35 Luncheon Presentation I : Esophageal Adenocarcinoma: Circulating Tumor Cells in Multimodal Treatment
Protocols
Jasmina Kuvendjiska, PhD, Surgery, Freiburg University
Our study was designed as a pilot study of the ESOPEC-Trial. We evaluated the presence and morphology of CTCs during the treatment period. The experimental results will be correlated with patients’ overall and relapse-free survival.
1:05 Luncheon Presentation II: Going Further with 3-color Crystal Digital PCR: Characterizing CNV,
Indels and Mutation
Linkage
Alexandra Martin, PhD, Application Specialist, Digital PCR, Stilla Technologies
1:35 Refreshment Break in the Exhibit Hall with Poster Viewing
2:05 Chairperson’s Remarks
Steven
A. Soper, PhD, Professor, Micro and Nanofabricated Tools for Biological Discovery and Medical Diagnostics, University of Kansas
2:10 Diagnosing Disease with Rare Circulating EVs: Finding Heterogeneous, Nanoscale Needles in a Nanoscale Haystack
David A. Issadore, PhD, Assistant Professor,
Bioengineering & Electrical & Systems Engineering, University of Pennsylvania
Circulating EVs contain a wealth of proteomic and genetic information, presenting an enormous opportunity for liquid biopsy. While microfluidics have been used to successfully isolate cells from complex samples, scaling these approaches
for EV isolation has been limited by the low throughput and susceptibility to clogging of nanofluidics. Moreover, the analysis of EV biomarkers is confounded by substantial heterogeneity between patients and within a disease itself.
To address these challenges, we developed a multichannel nanofluidic system to analyze crude clinical samples. Using this platform, we isolated EVs, profile the RNA cargo inside of these EVs, and apply a machine learning algorithm
to generate predictive panels that could provide useful diagnostics for applications in traumatic brain injury and pancreatic cancer using both murine models and clinical samples.
2:40 Single Cell Morphogenomic and Morphoproteomic Profiling of Liquid Biopsy in Prostate Cancer
Paymaneh D. Malihi, PhD Candidate,
USC Michelson Center for Convergent Bioscience
Peter Kuhn,
PhD, Dean’s Professor of Biological Sciences and Professor of Biological Sciences, Medicine, Biomedical Engineering, and Aerospace and Mechanical Engineering and Associate Director, The Bridge, University of Southern California
Tumor heterogeneity is prevalent in both treatment-naïve localized and end-stage metastasized prostate cancer, and may contribute to the broad range of clinical presentation, treatment response, and disease progression. High Definition-Single
Cell Analysis enables morphoproteomic and morphogenomic profiling of single cells from touch preparations of tissue cores as well as liquid samples. HD-SCA platform enables real-time molecular profiling of cells and has the potential
to elucidate the origin and evolution of metastatic tumor cells.
3:10 High Precision Isolation and Analysis of Exosomes
Daniel T. Chiu, PhD, A. Bruce Montgomery Professor of Chemistry and Bioengineering, University of Washington
We have recently developed microfluidic and nanofluidic systems for the isolation and analysis of exosomes, offering detailed molecular information with single-exosome resolution. Here, we will describe our technical approach, device
performance, and the new information we learned about exosomes as revealed by the new measurements.
3:40 Development and Performance of PlexBio’s IntelliPlex Lung Cancer Panel
Peter Friebe, PhD Senior Director Applications and Customer Support – US/EU, PlexBio Co., Ltd.
PlexBio developed the IntelliPlexTM Lung Cancer Panel as a rapid, comprehensive and cost-effective way to
interrogate patient samples with sensitivities as low as 0.1%. Based on πCodeTM technology,
the panel
assesses 36 DNA mutations (KRAS, NRAS, PIK3CA, BRAF and EGFR) and 19 gene variants (ALK, ROS1, RET, NTRK1 and MET).
3:55 Robust, Reliable and Fully Automated Isolation of Free Circulating DNA in Liquid Biopsy Applications
Andrea Ockhardt, PhD, Product Management, STRATEC Molecular Consumables GmbH
InviMag®DNA Kit enables efficient, standardized, fully automated purification of cfDNA fragments from 4 ml plasma samples. The InviGenius® PLUS simplifies
workflows by using a walk-away robotic system for up to 12 samples in parallel. cfDNA is concentrated in 40 µl for analysis.
4:10 St. Patrick’s Day Celebration in the Exhibit Hall with Poster Viewing
5:00 Breakout Discussions in the Exhibit Hall
Parallel Analysis of Circulating Biomarkers in Immunotherapy
Genevieve Boland, MD, PhD, Director, Melanoma Surgery Program, Massachusetts General Hospital; Director, Surgical Oncology Research Laboratories, Massachusetts General Hospital; Assistant Professor, Harvard Medical School; Associate
Member, Broad Institute
- Clinical application of blood-based biomarkers in melanoma
- Unmet clinical needs in blood-based biomarkers
- Microvesicle applications in immunotherapy
Clinical Utility and Impact of Liquid Biopsy
Rajan Kulkarni, MD, PhD, Assistant Professor, Dermatology and CEDAR/Knight Cancer Institute, Oregon Health and Science University
- Necessary features of technologies/tests for clinical utility
- Tumor information that is of clinical relevance
- Necessity for standardization
The Importance and Challenge in CTC Culture
Professor Yong-Jie Lu, MBBS, MD, PhD, Professor, Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London
- Why is CTC culture important?
- What is the challenge?
- Does it worth to try it?
- Alternative ways to avoid it?
- How can we success with CTC culture? The researcher, technology development and the funding supporter/policy marker.
Openness on collaboration for the benefit of all
Isolation and Analysis of CTCs
Min Yu, MD, PhD, Assistant Professor, Stem Cell Biology and Regenerative Medicine Member, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California
- Downstream analysis of circulating tumor cells
- Technologies for CTC isolation
- Experimental mouse models for metastasis analysis
- Using CTCs as liquid biopsy
6:00 Close of Day
Wednesday, March 13
7:30 am Registration Open and Morning Coffee (South Lobby)
8:00 Plenary Keynote Session (Room Location: 3 & 7)
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10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall
10:50 Chairperson’s Remarks
Stefanie Jeffrey, MD, John and Marva Warnock Professor,
Surgery; Chief, Surgical Oncology Research, Stanford University School of Medicine
11:00 Utilizing Extracellular Vesicles for Prediction and Monitoring of Immunotherapy Responses in Melanoma
Genevieve Boland, MD, PhD, Director, Melanoma Surgery Program, Massachusetts General Hospital; Director, Surgical
Oncology Research Laboratories, Massachusetts General Hospital; Assistant Professor, Harvard Medical School; Associate Member, Broad Institute
Immune checkpoint inhibitors (ICI) show therapeutic benefit in melanoma. We identified pretreatment and early on-treatment biomarkers that incorporate tumor and host immune status. Our findings suggest that peripheral blood-derived
exosomes may serve as a non-invasive biomarker to probe tumor and immune responses to ICI therapy, functioning as both a predictive marker of ICI responsiveness as well as a monitoring tool for tumor persistence and immune
activation.
11:30 Molecular Assessment of Circulating Extracellular Vesicles Toward Liquid Biopsy Diagnosis of Gastrointestinal Stromal Tumor and Ewing Sarcoma
Andrew K. Godwin, PhD, Chancellors Distinguished Chair in Biomedical Sciences and Endowed Professor and Director,
Molecular Oncology, Professor, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Deputy Director, University of Kansas Cancer Center
There is growing interest in exploiting circulating extracellular vesicles (EVs), primarily small bioactive nanovesicles (60–120 nm), known as exosomes, as developing sources of biomarkers for diagnosis and therapeutic response.
However, EVs are heterogeneous vesicles released by both healthy and tumors cells, with the vast majority of circulating vesicles being derived from normal host cells. To establish their utility as valuable tools for the diagnosis
of cancer and therapeutic monitoring of disease progression and response to therapy, we used molecular approaches to profile the proteome of Gastrointestinal Stromal Tumor (GIST)- and Ewing Sarcoma (EWS)-derived EVs, as well
as other types of cancer, which provided insights into the oncogenic cargo of these tumor-derived EVs. Using proteins enriched in these different sarcomas, we have developed microfluidic platforms and immunocapture approaches
to target tumor-associated EVs and in turn measure exosomal proteins and/or RNAs specific to a cancer subtype to further enhance the specificity of these liquid-based biopsies.
12:00 pm Personalized Detection and Monitoring of Lymphomas Using Circulating Tumor DNA
Ash Alizadeh, PhD, Associate Professor of Medicine, Divisions of Oncology & Hematology,
Stanford University School of Medicine
12:30 Enjoy Lunch on Your Own
1:10 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing
1:50 Chairperson’s Remarks
Shannon L. Stott, PhD, Assistant Professor, Department of Medicine, Massachusetts General Hospital, Harvard Medical School; BioMEMS Resource Center, The MGH Cancer Center
2:00 3D Microfluidic ex vivo Culture of Organotypic Tumor Spheroids to Model Immune Checkpoint Blockade
Russell W. Jenkins, MD, PhD, Member of the Faculty of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School
2:30 Patient-Derived Circulating Tumor Cells Inform Mechanisms of Metastasis
Min Yu, MD, PhD, Assistant Professor, Stem Cell Biology
and Regenerative Medicine Member, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California
Circulating tumor cells (CTCs) are expected to contain metastasis-initiating cells that can shed light on the mechanisms of cancer metastasis. However, due to limited patient-derived material, the metastatic capability of CTCs
has yet to be proved. Using our recently established patient-derived CTC lines, we found that different patient CTC lines demonstrated distinct metastatic tissue tropisms in immunodeficient mice and identified associated pathways
to specific organs via RNA-seq and ATAC-seq analysis.
3:00 From Sample-to-Single Cells-to-Answer – An Integrated Microfluidics Approach for Identifying Cancer Cells
Abraham
“Abe” Lee, PhD, William J. Link Professor and Chair, Department of Biomedical Engineering (BME); Professor, Mechanical & Aerospace Engineering; Director, NSF I/UCRC CADMIM Research Lab: Biomolecular Microsystems
and Nano Transducers (BioMiNT), University of California, Irvine
Liquid biopsy is performed by a microfluidic acoustic microstreaming device to isolate and target circulating tumor cells (CTCs) in whole blood. A key bottleneck is to identify the critical subpopulation of cells, often at single
cell resolution among billions of cells in circulation. An in vitro perfused vascularized 3D tissue platform can then determine which CTCs can be disseminated to distant tissues through the
circulatory system.
3:30 Session Break
3:40 Chairperson’s Remarks
Catherine Alix-Panabières, PhD, Director, Laboratory of Rare Human Circulating Cells (LCCRH), Pathology and Onco-Biology Department, University Medical Center of Montpellier
3:45 Expansion of Patient-Derived Circulating Tumor Cells from Liquid Biopsy
Chwee Teck (C.T.) Lim, PhD, NUS Society (NUSS) Professor, Department of Biomedical Engineering; Director, Biomedical Institute for Global Health Research and Technology; Founding Principal Investigator, Mechanobiology
Institute, National University of Singapore
Personalized therapy in cancer requires monitoring of patients’ individual response to treatment. One approach is to assess drug efficacy on circulating tumor cells (CTCs) obtained from patients’ blood samples (aka
liquid biopsy) following
ex vivo expansion into CTC clusters. We developed a simple microfluidics-based culture platform that allows co-culture of immune cells with CTCs (obtained after red blood cell lysis of patients’
blood) to promote CTC cluster formation.
4:15 Holy Grail and Big Challenge – Culture of Circulating Tumor Cells
Yong-Jie Lu, MBBS, MD, PhD, Professor, Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University
of London
Circulating tumor cells (CTCs) provide a minimally invasive approach to access living cancer cells. The culture of CTCs enables the investigation of their biological features, mechanisms of cancer metastasis and the opportunity
for
in vitro therapeutic sensitivity tests. Challenge to CTC culture includes their rarity, small proportion of viable cells and unclear favorable growth condition. I will give a brief summary of culture strategies
and our own experience.
4:45 Growing Organoids from CTCs: The Importance of CTC Input
Andrew Rhim, PhD, Associate Director for Translational Research Ahmed Center for Pancreatic Cancer Research Assistant Professor of Internal Medicine UT MD Anderson Cancer Center
Liquid biopsies have potential to inform personalized treatments and decision making in patients with cancer. While still in its infancy, the field has exploded, featuring numerous modalities and source material, including circulating
tumor cells (CTCs), circulating nucleic acids, exosomes, and others. CTCs, however, hold the greatest promise, as not only do they contain all the tumor-derived material that are in the circulation, but if they could be cultured
and propagated ex vivo, the prospect of functional analysis and direct drug combination testing could direct true individualized cancer care. Moreover, since CTCs are in the circulation, serial
assay of CTCs, during the throes of treatment, could allow for nimble decision-making to thwart resistance. The major hurdle in the application of CTCs in the clinic is the inability to establish CTC cultures. Our laboratory
has hypothesized that the major determinant of culture success is the number of CTCs seeded. This hypothesis is driven in part by evidence suggesting that a sub population of tumor cells retain stem cell like characteristics,
called cancer stem like cells. These cells are theorized to be required to initiate tumors and metastases since they possess the capacity for self-renewal. In current protocols, at most 60ml of blood is phlebotomized for CTC
isolation. However, we estimate that this yields far too few cancer stem like cells to achieve success in culture. Here we will review the efforts we have undertaken to achieve robust and routine cultures of CTCs, mostly by
focusing on dramatically increasing CTC input with less emphasis on epithelial cell purity. In so doing, our preliminary data suggest real promise in our approaches.
5:15 Close of Conference Program