Cambridge Healthtech Institute’s Second Annual
Circulating Tumor Cells
Evaluating Liquid Biopsies for Clinical Use
August 15-16, 2017 | Grand Hyatt Washington | Washington, DC
Non-invasive diagnostic testing is at the forefront of many precision medicine initiatives worldwide. Liquid biopsies may hold the key to this, allowing for diagnosis and monitoring of many diseases, specifically cancer, with no more than a blood-draw. However, there is still a need for more predictive and prognostic tools, a clearer understanding of the biology of these cells, and universal standards. Cambridge Healthtech Institute’s Second Annual Circulating Tumor Cells event will examine the potential of various circulating biomarkers including CTCs, ctDNA, DTCs, exosomes, and extracellular vesicles. Focus will be given to addressing tumor heterogeneity and determining relevant cells for treatment decisions. Finally, experts debate the viability of early disease detection along with the need for increased sensitivity and tools to correlate mutations with disease.
Final Agenda
Recommended Short Course(s)*
SC8: Clinical Validation of CTCs and Emerging Circulating Biomarkers
*Separate registration required
TUESDAY, AUGUST 15
7:30 am Main Conference Registration & Morning Coffee
8:30 Chairperson’s Opening Remarks
Daniel Danila, M.D., Genitourinary Oncology Service, Medicine, Memorial Sloan-Kettering Cancer Center
8:40 Building A Higher Bar for Circulating Tumor Cell-Based Diagnostics, Blood Profiling Atlas (BloodPAC) for Cancer - Former White House Cancer Moonshot Initiative
Hsian-Rong Tseng, Ph.D., Professor, Molecular and Medical Pharmacology, University of California Los Angeles
Yazhen Zhu, M.D., Ph.D., Project Scientist, Pharmacology, University of California Los Angeles; Medical Director, CytoLumina
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.
9:10 Microfluidic Approaches to Phenotypic and Genotypic Profiling of CTCs
Shana Kelley, Ph.D., Professor, Biochemistry, University of Toronto
Circulating tumor cells can be highly heterogeneous, and resolving their phenotypic properties is very important to understand their role in cancer progression. Genotypic information is also highly valuable and can inform therapeutic decisions. We are developing high-throughput microfluidic approaches that can report on CTC genotypes and phenotypes at the single-cell level. These tools allow dynamic CTC properties to be tracked in patients and animal models of cancer.
9:40 The Liquid Biopsy: Multimodal Spatio-Temporal Analysis of Cancer Progression Using Single Cell Proteo-Genomics
James Hicks, Ph.D., Professor, Biological Sciences, University of Southern California
It is rapidly becoming an article of faith that the ‘Liquid Biopsy,’ using a suite of cellular and molecular assays of blood or other body fluids will become a key component in our progress toward precision medicine and personalized treatment of cancer and other diseases. An array of blood-based assays are being developed that can provide a real time window into the course of the disease and its response to treatment. HD-SCA is an integrated proteo-genomic liquid biopsy platform for assessing cancer heterogeneity at both the cellular and molecular levels. We will describe its integration into the Blood Profiling Atlas of Cancer (BloodPAC) a joint industry and academic effort spawned from the Biden Cancer Moonshot initiative of 2016.
10:10 Coffee Break in the Exhibit Hall with Poster Viewing
10:55 Chairperson’s Remarks
Michele I. Vitolo, Ph.D., Assistant Professor, Physiology, University of Maryland School of Medicine
11:00 Validating a Biomarker Predictive of Clinical Outcome for Clinical Use
Daniel Danila, M.D., Genitourinary Oncology Service, Medicine, Memorial Sloan-Kettering Cancer Center
In addition to determining whether circulating tumour 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. In correlative studies with clinical findings, biopsy results, and imaging studies, molecular blood-based biomarkers are being optimized to predict and monitor the clinical benefit of novel treatments for patients with metastatic castration resistant prostate cancer.
11:30 Microfluidic Cell Tethering to Rapidly Measure Drug Responses in Patient Tumor Cells
Michele I. Vitolo, Ph.D., Assistant Professor, Physiology, University of Maryland School of Medicine
Nonadherent tumor cells display 4 phenotypes that are indicative of metastatic potential (microtentacles, clustering, deformability, stem cell sphere formation). However, technical challenges prevent high-resolution imaging of nonadherent tumor cells. Integrating hydrophobic lipids into an engineered microfluidic surface tethers tumor cells while preserving the dynamic behaviors of non-adherent tumor cells. This technology enables rapid testing of patient cells for responses to drug treatments that could influence CTC reattachment during metastasis.
12:00 pm Development of Circulating Molecular Predictors of Systemic Therapy Benefit in Men with Advanced Prostate Cancer
Andrew J. Armstrong, M.D., Associate Professor of Medicine; Co-Director, GU Oncology Research Program, Medicine and Surgery, Duke Cancer Institute
Recent advances in CTC and ctDNA technologies have enabled the assessment of rare splice variants, DNA mutations, and copy number analysis from circulating tumor cells or DNA/RNA fragments. These molecular biomarkers have been associated with the benefits of AR directed therapies such as enzalutamide and abiraterone as well as docetaxel chemotherapy. I will review these advances and ongoing validation studies to develop approved CTC or ctDNA-based predictive biomarkers in men with mCRPC.
12:30 The Power of CNA Profile Analysis after Pure, Single CTC Isolation and Recovery as a Clinical Tool
Nina Korzeniewski, Ph.D., National Scientific Affairs Liaison, Menarini Silicon Biosystems
The DEPArray™ platform can isolate and recover rare CTCs from an enriched blood sample for molecular diagnostics with unprecedented sensitivity. Downstream genetic analysis of these cells provides reliable insights into tumor drivers and mutational burden. Proof-of-concept for the prognostic potential of single-CTC analysis was recently published in a high-impact peer-reviewed journal. This talk will focus on the technological capabilities of the DEPArray™ and how the ability to isolate single tumor cells promotes patient stratification.
1:00 Luncheon Presentation: The Use of ctDNA as a Liquid Biopsy Tool in Cancer Research and Diagnostics
Harriet Wikman, Ph.D., Prof., Institute of Tumor Biology University, Medical Center Hamburg-Eppendorf
Circulating, tumor-free DNA (ctDNA) has received increasing attention due to its many potential clinical applications in the individual management of cancer patients. ctDNA is released from all metastatic sites and thus mirrors the heterogeneity of the different tumor cells, showing great power in detecting the occurrence of new mutations leading to a resistance against a given therapy. Here we present a new sensitive method to detect clinically relevant mutations in non-small cell lung cancer.
1:30 Refreshment and Cookie Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Matthew Young, Ph.D., Program Officer, Cancer Biomarker Research Group, Division of Cancer Prevention, National Cancer Institute
2:05 Deciphering the Code of Single EVs and RNPs Released from Glioblastoma Cells
Leonora Balaj, Ph.D., Instructor, Neurology, Massachusetts General Hospital, Harvard Medical School
Tumor cells release a variety of content in the extracellular milieu that includes lipid-based vesicles as well as ribonucleoprotein (RNP) complexes. Lipid vesicles are termed extracellular vesicles (EV) and include vesicles ranging from 50nm to 1µm and above. mRNA, miRNA, ncRNA DNA and proteins have all been described to be present in the extracellular environment but it is currently unknown the extent to which each subpopulation is present at any given time. Data will be reported on counting of these molecules from two glioblastoma cells under normal and hypoxic conditions.
2:35 Chemistry-Free Microfluidic Technologies to Sort Cells for Health and Disease
Utkan Demirci, Ph.D., Professor, Radiology, Stanford University
Micro- and nano-scale technologies can have a significant impact on medicine and biology in the areas of cell manipulation, diagnostics and monitoring. At the convergence of these new technologies and biology, our research is centered on enabling solutions to the real world problems at the clinic. Emerging nano-scale and microfluidic technologies integrated with biology offer innovative possibilities for creating intelligent, mobile medical lab-chip devices that could transform diagnostics and monitoring, tissue engineering and regenerative medicine. In this talk, we will first present an overview of our laboratory's work in these areas focused on applications in magnetic levitation methods for assembling cells and chemistry free sorting of rare cells from whole blood. Cells consist of micro- and nano-scale components and materials that contribute to their fundamental magnetic and density signatures. Previous studies have claimed that magnetic levitation can only be used to measure density signatures of non-living materials. Here, we demonstrate that both eukaryotic and prokaryotic cells can be levitated and that each cell has a unique levitation profile. Furthermore, our levitation platform uniquely enables ultrasensitive density measurements, imaging, and profiling of cells in real-time at single-cell resolution. This method has broad applications, such as the label-free identification and sorting of CTCs and CTM with broad applications in drug screening in personalized medicine. Second, we will present some of our efforts on developing new tools to isolate extracellular vesicles from blood, urine and cell cultures. I will also share some of the clinical implications of these technologies indicating the broader potential that chemistry-free and label-free microfluidic-based technologies have in medicine.
3:05 The Novel Association of Circulating Tumor Cells and Circulating Megakaryocytes with Prostate Cancer Prognosis
Yong-Jie Lu, MD, Ph.D., Reader Medical Oncology Centre for Molecular Oncology, Barts Cancer Institute
Previous studies on circulating tumor cells (CTCs) missed the proportion of CTCs undergoing epithelial to mesenchymal transition (EMT). We optimized a cell size and deformability based platform for the investigation of different subtypes of circulating tumor cells (CTCs) and other cells to evaluate their potential prognostic value of prostate cancer.
3:35 Improved Sensitivity for EGFR Mutation Profiles in Liquid Biopsies using the VTX-1 Liquid Biopsy System
Steve Crouse, Chief Commercial Officer, Vortex Biosciences, Inc.
The VTX-1 Liquid Biopsy System is a simple, fully automated system for isolating CTCs directly from whole blood. In this presentation we will demonstrate a workflow for the collection and EGFR mutation analysis of both cfDNA and CTCs from a single blood tube using the VTX-1 platform.
3:50 An Open Platform for Single-Cell Isolation
Barbara McIntosh, Vice President, Business Development, Scienion
Following the simple liquid handling pipetting concept of aspirate and dispense, we have developed an automated system to dispense single cells. Aspirate as little as 5 ul of a cell suspension, and dispense 300 pl droplets containing single cells onto any target (microtiter plates, slides, microwells) with full viability
4:05 Refreshment Break in the Exhibit Hall with Poster Viewing
4:50 PANEL DISCUSSION: Early Detection with Liquid Biopsy: Pipe Dream or Possibility?
Moderator: Lynn R. Sorbara, Ph.D., Program Director, Cancer Biomarker Research Group, National Cancer Institute
- Challenges
- Gaps
- Wish list
- Can existing technologies be adapted?
Panelists:
Daniel Danila, M.D., Genitourinary Oncology Service, Medicine, Memorial Sloan-Kettering Cancer Center
Utkan Demirci, Ph.D., Professor, Radiology, Stanford University
James Hicks, Ph.D., Professor, Biological Sciences, University of Southern California
5:50 Wine & Cheese Pairing Welcome Reception in the Exhibit Hall with Poster Viewing
6:50 Close of Day
WEDNESDAY, AUGUST 16
7:15 am Registration
7:30 Problem-Solving Breakout Discussions with Continental Breakfast
Challenges to Bring Liquid Biopsy to Early Detection
Moderator: Lynn R. Sorbara, Ph.D., Program Director, Cancer Biomarker Research Group, National Cancer Institute
- What are the technological issues/gaps that make early detection of cancer so challenging?
- How can we address the biological challenges of low concentrations of target analytes?
- Detection of targets vs. clinical correlation and relevance? How can we address this?
- Is it time for a “bake-off?”
- Is industry-academic alliances the new model for liquid biopsy?
Developing Circulating Biomarkers for Clinical Practice
Moderator: Andrew J. Armstrong, M.D., Associate Professor of Medicine; Co-Director, GU Oncology Research Program, Medicine and Surgery, Duke Cancer Institute
- Prognostic vs. Predictive markers: where is the clinical utility?
- Do CTC platforms matter?
- Automated vs observer-dependent calls: advantages and disadvantages
- How can we best incorporate circulating biomarkers into clinical trials?
8:55 Chairperson’s Opening Remarks
9:00 The Molecular Characterization of CTC Subsets: The Future of Cancer Diagnostics
Dario Marchetti, Ph.D., Director, Center of the Biomarker Research Program, The Methodist Hospital Research Institute
The identification of CTCs across multiple solid tumors and their appearance in peripheral blood early in the metastatic cascade provides a window of opportunity to prevent metastatic recurrence by eliminating these “seeds” of fatal metastases. We report the molecular characterization of CTCs and signaling pathways associated with BCBM (breast cancer brain metastasis) based on comprehensive analyses of breast cancer patient-derived CTC transcriptomes. We have identified a unique CTC gene signature that is distinct from primary breast cancer tissues and valid across all molecular subtypes but contrasting upon BCBM onset. Further, we report that heightened genomic instability may typify CTC sub-populations that have overcome metabolic/mitotic dormancy in the brain micro-environment leading to overt metastases.
9:30 Redefining Circulating Tumor Cells and Enabling Liquid Biopsy: Biological and Clinical Advances Arising from the Merger of the CELLSEARCH® and DEPArray™ Technologies
Mark C. Connelly, Ph.D., Chief Industrial Operations, R&D Officer, US, Menarini Silicon Biosystems, Inc.
The prognostic power of Circulating Tumor Cells (CTC) measured using CELLSEARCH®, is arguably the most reproducible and independently verified finding in the field of CTC analysis. The ability to use DEPArray to do complete molecular analysis on individual, or populations, of CTCs with 100% purity from samples of complex cellularity is also well established. Combining these two technologies is now giving rise to unprecedented understanding of CTC heterogeneity, emerging CTC phenotypes, and exiting new prospects for the researchers and clinicians.
10:00 ScreenCell Isolation of Circulating Tumour Cells, Combined with TeloView(TM) Genomic Stability Profiling, to Predict Clinically Relevant Prostate Cancer
Kevin Little, Ph.D., CSAP, CSO, 3D Signatures Inc.
3D Signatures has developed the TeloView (TM) platform technology that visualizes and evaluates the degree of genomic instability in single cells. With clinical evidence across 14 cancers and neurological disorders, TeloView(TM) profiles have identified an individual’s likelihood of relapse, disease progression, drug response, disease severity, or need for therapy. 3D Signatures has combined TeloView(TM) with the ScreenCell filtration device, for the isolation of circulating tumour cells (CTCs) from blood, to accurately and non-invasively assess cancer staging and progression.
10:15 Delivering on the Promise of Liquid Biopsy
Eric Kaldjian, MD, CMO, RareCyte, Inc.
The potential for non-invasive tests that provide equivalent research and diagnostic value as can be obtained from tissue biopsies is real, but not yet realized. Tissue biopsies allow for identification, phenotyping and molecular analysis of cancer and associated cells. The RareCyte platform has been designed to reflect tissue analyses in the identification, multi-parametric characterization and single cell molecular interrogation of rare cells in liquid biopsies and other sample types. Applications to be presented include genomic assessment of heterogeneity in individual breast cancer circulating tumor cells at multiple time points during treatment, development of a CDx-type assay to identify the presence of a drug target on CTCs, and identification of rare antigen-specific T cells. These examples demonstrate progress toward the fulfilling the promise of liquid biopsy.
10:30 Coffee Break in Exhibit Hall with Poster Viewing
1:05 pm Luncheon Presentation: Inroads into Cancer Patient Care with Digital PCR
George Karlin-Neumann, Ph.D., Director, Scientific Affairs, The Digital Biology Center, Bio-Rad
Over the past 5 years, Droplet Digital PCR technology has proven to be a highly sensitive and accurate means for the detection and quantification of nucleic acid markers in 1000’s of labs worldwide. Its widespread adoption in liquid biopsy studies and its demonstrated interlab reproducibility have propelled it into clinical use for cancer patients in cutting-edge diagnostic labs. Where biomarkers of interest are known, ddPCR provides affordable and rapid answers to aid in clinical decision-making.
1:35 Ice Cream and Cookie Break in the Exhibit Hall with Poster Viewing
1:35 Close of Circulating Tumor Cells