The promise of cancer molecular markers is that they allow diagnosis and targeted therapy of tumors and provide important insights on drug resistance. They also allow the segmenting of patient populations to receive immunotherapy. The Cancer Molecular Markers conference track will highlight the newest kinds of cancer markers and illustrate how they will be deployed in the clinic. These include non-coding RNA, exosomal microRNAs, circulating tumor cells, cell-free DNA, stem cells, circulating endothelial cells, extracellular vesicles and more.
Monday, February 20
10:30 am Conference Program Registration Open
11:50 Chairperson’s Opening Remarks
Stefanie Jeffrey, M.D., John and Marva Warnock Professor, Surgery; Chief, Surgical Oncology Research, Stanford University School of Medicine
12:00 pm Smart Tumors, CTCs and Liquid Biopsies
George W. Sledge, M.D., Professor, Medicine; Chief, Division of Oncology, Stanford University School of Medicine
Cancers kill because they are resistant to currently available therapies. The promise of CTC and ctDNA technologies is that they will allow either earlier diagnosis of small tumors, or provide crucial evidence regarding drug resistance at a point where that resistance is reversible. What are the prospects for CTC and ctDNA technologies reversing potentially lethal drug resistance, and how will we employ them in the clinic?
12:30 Isolation and Molecular Characterization of Breast Cancer Stem Cells
Max S. Wicha, M.D., Madeline and Sidney Forbes Professor, Oncology; Founding Director Emeritus, University of Michigan Comprehensive Cancer Center
There is substantial evidence that tumors are driven by a subpopulation of cells that display stem cell properties and that these cells mediate tumor metastasis and contribute to treatment resistance. A number of agents designed to target these cancer stem cells are now in early stage clinical trials. The development of robust platforms to isolate and molecularly characterize circulating tumor cells at single cell resolution should greatly facilitate these studies.
1:00 Session Break
1:10 Luncheon Presentation I: CTC Enrichment by Parsortix™- Clinical Applications
Robert Zeillinger, Ph.D., Associate Professor, Molecular Oncology Group, Medical University of Vienna
1:40 Luncheon Presentation II to be Announced
2:10 Session Break
2:30 Chairperson’s Remarks
Klaus Pantel, M.D., Professor and Founding Director, Institute of Tumor Biology, University, Medical Center Hamburg-Eppendorf
2:40 Tumor-Educated Platelets as a Blood-Based Liquid Biopsy Platform for Cancer Diagnostics
Myron G. Best, Ph.D. Student, Neurosurgery, Cancer Center Amsterdam, VU University Medical Center Amsterdam, The Netherlands
Blood-based ‘liquid biopsies’ provide a means for minimally invasive molecular diagnostics. Confrontation of blood platelets with tumor cells via transfer of tumor-associated biomolecules (tumor-educated platelets; TEPs) is an emerging concept. We performed RNA-sequencing of >1000 platelet samples covering multiple tumor types. Our results indicate that platelets provide a valuable platform for cancer diagnostics. The unprecedented ability of TEPs to pinpoint the location of the primary tumor advances the use of liquid biopsies for cancer diagnostics.
3:10 Unveiling the Circulating Tumor Endothelial Cell Cluster
Min-Han Tan, Ph.D., Principal Investigator, Biodevices and Diagnostics, Institute of Bioengineering and Nanotechnology
Circulating cell clusters have been reported for decades in cancer patients as malignant entities with a key role metastasis. Contrary to this consensus, we describe a discrete population of tumor-derived circulating cell clusters with similar cytomorphology and EMT marker expression, but with origins traced instead to the tumor endothelia.
3:40 About Chomsky, DNA Patterns, Non-Coding RNAs and Cancer Patients
George A. Calin, M.D., Ph.D., Professor, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center
The newly discovered differential expression in numerous tissues, key cellular processes and multiple diseases for several families of long and short non-codingRNAs (ncRNAs, RNAs that do not codify for proteins but for RNAs with regulatory functions), including the already famous class of microRNAs (miRNAs) strongly suggest that the scientific and medical communities have significantly underestimated the spectrum of ncRNAs whose altered expression has significant consequences in diseases.
4:10 Recovery & State-of-the-Art Molecular Analysis of Single (Pure) CTCs using DEPArray Based Technology
Farideh Bischoff, Ph.D., Chief Clinical Development Officer, North America Menarini Silicon Biosystems
DEPArray™ Platform delivers precision in the preparation circulating tumor cells for MDx. Complete workflows have been developed for the recovery of pure single CTCs that are amenable to downstream NGS approaches, including targeted panel and low pass copy number analysis.
4:25 Sponsored Presentation (Opportunity Available)
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, February 21
7:30 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
Stefanie Jeffrey, M.D., John and Marva Warnock Professor, Surgery; Chief, Surgical Oncology Research, Stanford University School of Medicine
10:15 Single-Cell Phenotypic Analysis of Circulating Tumor Cells
Dino Di Carlo, Ph.D., Professor, Bioengineering, California NanoSystems Institute; Director, Cancer Nanotechnology Program, Jonsson Comprehensive Cancer Center, University of California, Los Angeles
We have developed several workflows for integrating Vortex trapping technology with downstream phenotypic analysis of single circulating tumor cells (CTCs). I will present our results in analyzing single-cell secretions from CTCs in an automated microfluidic workflow and proof of concept clinical studies to evaluate expression levels programmed death ligand 1 (PD-L1) on Vortex-isolated CTCs from non-small cell lung cancer patients on checkpoint inhibitor therapy.
10:45 Circulating Tumor DNA Analysis – Clinical Impact
John Strickler, M.D., Assistant Professor, Medicine, Duke University Medical Center
Interest in ctDNA to diagnose, monitor, and profile solid tumors has surged. The increased use of ctDNA reflects a desire to minimize procedural risk to the patient, while applying therapies tailored to a patient’s specific tumor profile. Already, ctDNA is routinely used to guide therapeutic decision-making, and to identify patients for clinical trials. In this presentation, the opportunities and challenges of utilizing ctDNA in the clinic will be discussed.
11:15 Microfluidics for the Efficient Selection of Disease-Associated Extracellular Vesicles from Plasma
Steven A. Soper, Ph.D., Foundation Distinguished Professor, Department of Chemistry, Department of Mechanical Engineering; Director, Center of BioModular Multi-Scale System for Precision Medicine, The University of Kansas
Liquid biopsies are generating interest within the biomedical community due to the simplicity for securing important markers. These circulating markers consist of CTCs, cell free DNA and extracellular vesicles. We are developing a microfluidic that can process plasma and efficiently search for disease-associated extracellular vesicles comprising divergent subpopulations. These subpopulations emanate from different cancer cell types and can supply complimentary clinical information.
11:45 A Novel, High Yield, High Complexity, and Scalable Active-Extraction of Circulating Cell-Free DNA (ccfDNA) from Stabilized Plasma
Hamid Khoja, Ph.D., Principal Scientist, Research & Development, Covaris Inc.
In this talk we present data illustrating the effectiveness of the Covaris Adaptive Focused Acoustics™ (AFA) enabled truXTRAC ccfDNA active extraction method. Specifically designed for dissociating and extracting ccfDNA from histone-ccfDNA and other protein-ccfDNA covalently-linked complexes which occur in BCT®-stabilized plasma, the magnetic bead based truXTRAC ccfDNA enables scalable and automatable high throughput sample processing. Furthermore, DNA sequencing confirmed that truXTRAC ccfDNA processed samples resulted in higher library complexity, mapped reads, coverage uniformity, and variant detection sensitivity when compared to passive ccfDNA extraction methods.
12:00 pm VTX-1 Liquid Biopsy System: The Next Step in CTC Isolation
Steve Crouse, M.S., MBA, Chief Commercial Officer, Vortex Biosciences, Inc.
The VTX-1 Liquid Biopsy System isolates and collects intact CTCs directly from whole blood in as little as 1 hour. Clinical data will demonstrate how the proprietary approach results in the capturing of more clinically relevant CTCs with >60% CTC recovery and best in class CTC purity.
12:15 Session Break
12:25 Luncheon Presentation I: Highly Sensitive Isolation and Molecular Characterization of CTC for Early Detection of Tumor Invasion
Patrizia Paterlini-Brechot, M.D., Ph.D., Professor, Faculty of Medicine, University Paris Descartes
ISET allows to isolate fixed and live tumor cells with sensitivity down to one per 10 mL of blood. We show NGS analyses of single cells enriched by ISET® and of tumor cells before and after isolation and culture.
12:55 Luncheon Presentation II: Improving NGS-Based Liquid Biopsy Mutation Detection with Anchored Multiplex PCR
Josh Stahl, MSc, MBA, CSO, General Manager, ArcherDX
Liquid biopsies have the potential to be a less invasive method than traditional biopsies to detect advanced solid tumor mutational status. Anchored Multiplex PCR (AMP™) is target enrichment chemistry for NGS that is uniquely suited for highly fragmented material such as liquid biopsy-derived ctDNA. AMP-based ctDNA library preparation uses molecular barcoded adapters to remove PCR duplicates, correcting for both PCR and sequencer-derived sequencing errors while enabling accurate allele frequency quantitation.
1:25 Refreshment Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Steven A. Soper, Ph.D., Foundation Distinguished Professor, Department of Chemistry, Department of Mechanical Engineering; Director, Center of BioModular Multi-Scale System for Precision Medicine, The University of Kansas
2:10 Comparison of Different CTC Isolation Technologies in the Context of Clinical Utility
Pamela Paris, Ph.D., Professor, Urology, University of California, San Francisco
This presentation will provide an overview of some of the CTC platforms available today. The strengths and limitations of the CTC platforms will be discussed based on first-hand use in the laboratory. Examples will be provided for each platform’s potential clinical utility.
2:40 Integrated Extracellular Vesicle Profiling for Minimally Invasive Diagnosis and Early Detection of Cancer
Andrew K. Godwin, Ph.D., Chancellors Distinguished Chair, Biomedical Sciences and Endowed Professor, Professor and Director of Molecular Oncology, Pathology and Laboratory Medicine; Deputy Director, The University of Kansas Cancer Center; Director, Biospecimen Shared Resource Kansas Bioscience Authority; Eminent Scholar, University of Kansas Medical Center
Extracellular vesicle (EV), primarily nano-sized vesicles of endocytic origin referred to as exosomes, are produced and released by most cells types under normal physiologic and in diseased states. Considered little more than garbage cans whose job was to discard unwanted cellular components, recent discoveries have sparked interest as circulating biomarkers. Ways to exploit these circulating EVs and their payloads of proteins and nucleic acids using miniaturized biomedical assays will be discussed.
3:10 Orthogonal Endpoints in Prostate Cancer Circulating Tumor Cell Biomarkers
Joshua M. Lang, M.D., MS, Assistant Professor, Medicine, Carbone Cancer Center, University of Wisconsin
Prostate cancer is a heterogeneous disease with complex, intersecting mechanisms of resistance to targeted therapies. Prospective clinical trials interrogating CTC biomarkers across protein, gene expression and genomic endpoints identify acquired resistance mechanisms and pharmacodynamic biomarkers.
3:40 3D Telomere Signatures Indicate Prostate Cancer Progression in CTC’s Isolated with ScreenCell Technology
Sabine Mai, Ph.D., Professor, University of Manitoba, Director, The Genomic Centre for Cancer research and Diagnosis, Manitoba Institute of Cell Biology/RIOH, University of Manitoba
Using 3D Telomere Technology and circulating tumor cells isolated using the ScreenCell device, we examined intermediate risk prostate cancer patients prior to their radical prostatectomy. 3D nuclear telomeric profiles correctly identified patients with stable vs. progressive disease prior to RP.
4:10 Hollywood Oscar Dessert Reception 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. Pre-registration to sign up for one of the topics will occur a week or two prior to the Event via the App.
Making Omic Data Clinically Actionable
Elizabeth Worthey, Ph.D., Faculty Investigator, Clinical Informatics Director, and Adjunct Associate Professor, Software Development and Informatics, Pediatrics and Genetics, HudsonAlpha Institute for Biotechnology
- Discuss the guidelines to standardize interpretation and reporting of genomic test results
- Criteria for reporting
- How to make omic data clinically actionable
The Use of RNA Biomarkers for Blood-Based Cancer Diagnostics
Myron G. Best, Ph.D. Student, Neurosurgery, Cancer Center Amsterdam, VU University Medical Center Amsterdam, The Netherlands
- Available biosources and biomolecules for blood-based RNA biomarkers
- Techniques/approaches to measure RNA in these biosources
- Most potential applications and approaches for blood-based RNA biomarkers
- Combined cfDNA/cfRNA tests for cancer diagnostics
Cell-Free DNA Profiling In The Clinic
Dana W. Y. Tsui, Ph.D., Assistant Attending Geneticist; Member, Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center
- Applications for molecular profiling in oncology
- Applications for monitoring treatment efficacy (e.g. transplantation)
- Practical considerations (Sample processing, logistics and quality controls)
Recent FDA Feedback, Tips and Trends for IVDs
Gail Radcliffe, President, Consulting, Radcliffe Consulting, Inc.
- RTA Checklist: tips for jumping over the first hurdle
- Next-Gen Testing: regulation snafu
- CLIA Waiver: simple and low risk of erroneous result
- De Novo: providing rationale to support De Novo classification
6:00 Close of Day
Wednesday, February 22
7:00 am Registration Open
7:00 Breakfast Presentation (Sponsorship Opportunity Available) or Morning Coffee
8:00 Plenary Keynote Session
10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall
10:50 Chairperson’s Remarks
Jianda Yuan, M.D., Ph.D., Director, Translational Immuno-Oncology Research, Early Clinical Oncology Development, Merck & Co., Inc.
11:00 Co-Presentation: Next Generation Biomarkers for the Era of Combination Cancer Immunotherapy
Jianda Yuan, M.D., Ph.D., Director, Translational Immuno-Oncology Research, Early Clinical Oncology Development, Merck & Co., Inc.
Sarah Javaid, Ph.D., Senior Scientist, Discovery Pharmacogenomics, Genetics and Pharmacogenomics, Merck & Co., Inc.
Combination approaches are the keys to improving clinical response. From preclinical immune-oncology mouse models to patients enrolled on clinical trials, novel high throughput technologies enable us to understand the mechanisms underlying the complex interactions between the immune system and cancer, identify predictive biomarkers for the patients who will most likely benefit from current immunotherapies, avoid immune-related adverse events and guide the future combination cancer immunotherapy.
11:30 Precision Immunotherapy: The Challenge of Converting Complex Predictive Biomarkers into Practical Companion Diagnostics
Ruslan Novosiadly, Senior Research Advisor, Cancer Immunobiology, Biomarkers, Eli Lilly
Early immunotherapies have produced dramatic results for some patients, but future immunotherapies likely need to be guided by diagnostics to benefit more patients. Properly targeting immunotherapy requires incorporating into clinical practice complex diagnostics which can assess host immune response in addition to cancer biology itself. “Precision Immunotherapy” requires discovery of appropriate predictive biomarkers and incorporating them into practical companion diagnostics which will be adopted by practitioners.
12:00 pm Utility of Quantifying Circulating Lymphocyte Populations as Pharmacodynamic Biomarkers in Trials of Immune Oncology Therapeutics
Nathan Standifer, Ph.D., Scientist II, Clinical Pharmacology and DMPK, MedImmune
Immune oncology (IO) therapeutics are directed at inducing immune responses against tumor cells. Intrinsic to this mechanism of action is the activation of circulating immune cells, which can be most effectively monitored using flow cytometry-based assays. In this presentation, aspects of assay development, validation, implementation and analysis of clinical flow cytometry datasets will be discussed. Results from clinical trials of IO as single agents or in combination with other IO will be shown and strategies for interpretation and post-hoc analyses will be detailed.
12:30 Session Break
12:40 Luncheon Presentation: Driver-Map™ Genome-Wide Expression Profiling Solution for Biomarker Discovery
Alex Chenchik, Ph.D., President & Scientific Director, Cellecta, Inc.
Driver-Map Genome-Wide Expression Profiling solution combines the sensitivity of multiplex PCR with the dynamic range of NGS. With 10 pg total RNA, a 100-fold greater sensitivity over RNA-Seq. Applications include complex samples like whole blood, tumor microenvironment characterization, xenografts, etc.
1:10 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing
1:50 Chairperson’s Remarks
Luis A. Diaz, M.D., Associate Professor, Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
2:00 Genomic Features of Resistance to Anti-PD-1 Immunotherapy
Jesse Zaretsky, UCLA-Caltech Medical Scientist Training Program, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles
Resistance to anti-PD1 immunotherapy can take the form of either innate lack of response, or late acquired resistance after initial tumor regression. For the former, we define a transcriptomic mesenchymal and wound-healing associated expression signature enriched among non-responders in pre-therapy tumors from metastatic melanoma patients. For the latter, exome sequencing of paired pre/post relapse tumors revealed loss of function mutations in the interferon response pathway and antigen presentation machinery.
2:30 Shaping of Immunotherapy Response by Cancer Genomes
Rajarsi Mandal, M.D., Head & Neck Surgical Oncology Fellow; Professor, Surgery, Memorial Sloan Kettering Cancer Institute
Immune checkpoint blockade is a promising approach for the treatment of human malignancies. For example, treatment of patients with advanced lung cancers and melanoma have resulted in improved response rates and durable disease control. However, the extent to which patients derive benefit is diverse and the determinants that drive response to therapy are ill-defined. We have sought to define the genomic determinants of response to immune checkpoint blockade therapies such as anti-CTLA-4 and anti-PD-1. Our work has shown that tumor mutational burden, clonality, and mutational landscape features help dictate clinical response. Mutations in genes that are part of the antigen presentation machinery are rare but can be preferentially downregulated in tumors. Reexpression of genes in the MHC antigen presentation pathway by treatment with epigenetic therapy synergizes with immune checkpoint blockade to boost anti-tumor responses.
3:00 Addressing the Challenges Associated with Immuno-Therapy Biomarker Testing
John Leite, Ph.D., Vice President, Oncology, Market Development & Product Marketing, Illumina, Inc.
Recent developments in immuno-therapy have yielded exciting and promising results, but have also highlighted the need for effective predictive solutions. In this session, we will discuss the inherent testing challenges facing translational researchers, and future challenges facing clinicians seeking to implement these solutions into routine clinical practice.
3:30 Session Break
3:40 Chairperson’s Remarks
Gerald J. Kost, M.D., Ph.D., M.S., FACB, Director, POC Testing Center for Teaching and Research (POCT•CTR), Pathology and Laboratory Medicine, School of Medicine, University of California, Davis
3:45 Deciphering the Code of Single EVs and RNPs Released from Glioblastoma Cells
Leonora Balaj, Ph.D. Research Fellow, 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.
4:15 Exosomal MicroRNAs Regulate the Biology of the Tumor Microenvironment
Muller Fabbri, M.D., Ph.D., Assistant Professor, Pediatrics and Molecular Microbiology & Immunology, Pediatric Hematology/Oncology, Children’s Hospital Los Angeles - University of Southern California
MicroRNAs can be shuttled between different cell populations of the Tumor Microenvironment. The exchange of microRNAs affects the phenotype of cancer cells and surrounding cells contributing to cancer growth and resistance to therapy. Conversely, immune cells can affect cancer growth by releasing specific exosomic microRNAs. This lecture will focus on the role of exosomal microRNAs as central determinants of the biology of the tumor microenvironment and of cancer resistance.
4:45 Noncoding RNAs as Biomarkers in Gastrointestinal Cancer
Ajay Goel, Ph.D., Professor and Director, Center for Gastrointestinal Research, and Director, Center for Epigenetics, Cancer Prevention and Cancer Genomics, Baylor Research Institute, Baylor University Medical Center
Noncoding RNAs (ncRNAs) are emerging as important regulators of gene expression in cancer. Overexpression of specific noncoding RNAs (including microRNAs, SnoRNAs, piRNAs and circular RNAs) has been linked to the stepwise disease progression in colorectal cancer (CRC). Given their cancer-specific pattern of expression, remarkable stability and presence in blood and other body fluids, ncRNAs are considered to be highly promising cancer biomarkers. Accumulating evidence firmly supports the existence of unique ‘ncRNA signatures’ that can not only facilitate earlier detection of the tumor, but can also assist in predicting disease recurrence and therapeutic outcome to current treatment regimens.
5:15 Close of Conference Program
Stay on for these Tri-Conference Symposium, taking place at February 23-24, 2017 at Moscone South Convention Center
Circulating Cell-Free DNA