Predictive cancer biomarkers hold the promise of early cancer detection, personalized treatment, and accurate patient monitoring. Cambridge Healthtech Institute’s Ninth Annual Predictive Cancer Biomarkers symposium will focus on current research regarding tumor pathways and biomarker discovery, the progress toward clinical applications such as early detection and therapy monitoring, and case studies focusing on clinical utility and actionability, how many patients benefit from these assays, the role of genetic counselors, and practicality of funding and reimbursement. FDA validation will also be discussed. Join top cancer researchers and your peers to examine discoveries, best practices, and future directions.
FRIDAY, AUGUST 26
8:00 am Registration & Morning Coffee
8:25 Chairperson’s Opening Remarks
Anuradha Murali, Ph.D., MSCR, Clinical Trial Manager, Gastroenterology Associates of Orangeburg
8:30 Integrated Genomic Analysis of Pancreatic Ductal Adenocarcinomas Reveals Genomic Rearrangement Events as Significant Drivers of Disease
George Vasmatzis, Ph.D., Director, Biomarker Discovery Program, Center for Individualized Medicine, Mayo Clinic
In this study, we performed mate pair sequencing (MPseq) on genomic DNA from 24 PDAC tumors, including 15 laser-captured microdissected PDAC and 9 patient-derived xenografts, to identify genome-wide rearrangements. Large genomic rearrangements with intragenic breakpoints altering key regulatory genes involved in PDAC progression were detected in all tumors. SMAD4, ZNF521, and FHIT were among the most frequently hit genes. Conversely, commonly reported genes with copy number gains, including MYC and GATA6, were frequently observed in the absence of direct intragenic breakpoints, suggesting a requirement for sustaining oncogenic function during PDAC progression. Additionally, a number of potentially targetable amplifications and fusions have been observed opening the possibility to genomically driven targetable treatment in PDAC.
9:00 Towards Cancer Diagnostics Based on Interphase Spatial Genome Positioning
Karen Meaburn, Ph.D., Research Scientist, NCI, NIH
The genome is non-randomly organized in the cell nucleus. We have identified several genes that robustly alter position in breast or prostate cancer. These genes, used singularly or in combination, are able to distinguish cancer from normal tissue with high accuracy. We are working towards exploiting these changes in positioning patterns to develop a novel diagnostic strategy for the detection of cancer.
9:30 FEATURED PRESENTATION: Ultraconserved Elements: The Enigma and the Potential
C.-Ting Wu, Ph.D., Professor, Genetics, Harvard Medical School
Ultraconserved elements (UCEs) are DNA sequences that have been perfectly (100%) conserved for 300-500 million years. Because neither protein coding, nor enhancer, nor transcription factor binding, nor promoter regions require such conservation, the mere existence of UCEs has been a long debated conundrum. We propose that UCEs contribute to genome integrity and, hence, may provide a strategy by which otherwise healthy tissues can be culled of cells harboring deleterious rearrangements.
10:00 A Novel rRNA Depletion Method to Enable Whole Transcriptome Analysis of Single Cells with RNA-Seq
Maureen Peterson, Ph.D., Product Development Scientist, Research & Development, NuGEN Technologies
RNA-Seq analyses of transcripts from large numbers of cells often masks biologically relevant differences that occur in individual cells. Understanding RNA expression in a single cell has great potential for biomarker development, and monitoring disease progression and therapy. We describe a method for generating RNA-Seq libraries from single cells that enables removal of specific transcripts without perturbing the original total RNA population, providing a solution for biomarker discovery and diagnostic applications using extremely limited samples.
10:30 Coffee Break
11:00 Circulating Cell-Free DNA, RNA and Exosomes –Key Biomarkers for Early Cancer Detection and LiquidBiopsy Diagnostics
Michael J. Heller, Ph.D., Professor, Bioengineering & Nanoengineering, University of California San Diego
Exosomes and their associated RNA and proteins, as well as circulating cell-free DNA are now considered to be important key biomarkers for cancer diagnostics ranging from early detection to liquid biopsy for patient management and therapy monitoring. Nevertheless, the isolation and detection of these biomarkers, exosomes in particular, require considerable time and effort which greatly limits their practical, reliable and more widespread use in cancer diagnostics. Using a DEP device, we are now able to isolate all of these key biomarkers, including exosomes, in 15-20 minutes from 25-50ul of blood, plasma or serum. In the case of glioblastoma exosomes isolated from plasma, specific surface and interior proteins CD63 and TSG101 could then be detected by immunofluorescence, and EGFRvlll mutations in mRNA were detected by RT-PCR.
11:30 Using Molecular Profiling in Early Clinical Trials
Barbara Conley, M.D., Associate Director, Cancer Diagnosis Program, Division of Cancer Treatment & Diagnosis, National Cancer Institute (NCI)
The talk will inform the audience of the thinking behind the design of the NCI-MATCH trial, which profiles a fresh biopsy of patients with malignancies who have progressed on standard treatment. This trial uses a validated locked platform of NGS, supplemented by IHC assays, to assign patients to treatment arms based on molecular eligibility criteria, regardless of histology. The trial accrued very robustly from first opening. The MATCH trial is a signal-finding trial based on levels of evidence for both the treatments and the molecular eligibility criteria. Lessons learned will be presented. As such it represents a type of clinical validation of potentially predictive molecular features, and presents the opportunity to learn about the effect of co-mutations on response rate.
12:00 pm Tumor Heterogeneity and the Course of Mutation Detection Following Treatment
Jennifer Morrissette, Ph.D., Scientific Director, Clinical Cytogenetics Laboratory; Clinical Director, Center for Personalized Diagnostics (CPD), University of Pennsylvania School of Medicine
The routine implementation of NGS in the diagnosis and decision making process of malignancies has increasingly become part of routine clinical care. For most malignancies tested, only one specimen is received; however there are increasingly more patients assessed at additional time points throughout their disease allowing for tracking of the response to targeted and traditional chemotherapy. In hematological malignancies there has been the greatest uptake for the use of NGS to track disease response, as these patients can be serially assessed. This talk will focus on the mutation patterns before and after treatment and patient response to targeted therapies, on clinical trials and off-label.
12:30 Non-Bisulfite Epigenetic Profiling of DNA Methylation Enables Epigenetic Diagnostic Biomarker Discovery
Adam Marsh, Ph.D., CSO, Genome Profiling LLC
We have developed a novel computational platform for NGS quantitative DNA methylation profiling. This diagnostic platform has great utility for CDx applications. A use case in patients with Acute Myeloid Leukemia shows high confidence in pre-treatment identification of responders and non-responders to a hypomethylating drug therapy.
12:45 Sponsored Presentation (Opportunity Available)
1:00 Luncheon Presentation: Elucidation of Circulating miRNA Biomarkers in Oral Cavity Cancer Utilizing Multiplex qPCR Array
Eric Yang, Ph.D., Vice President, Quark Biosciences
Numerous publications have illustrated that microRNAs can be of diagnostic, prognostic and predictive values in the field of oncology. Utilizing PanelChip™, a qPCR array technology developed by Quark Biosciences, we’ve looked at the level of 160 microRNAs in the plasma of oral cavity cancer patients before and after surgery. Preliminary result suggests that PanelChip™ can be of a powerful tool to screen and validate cell-free miRNA biomarkers for translational medical researchers.
1:30 Session Break
2:00 Chairperson’s Remarks
Chair to be Announced, Stilla Technologies
2:05 Crucial Considerations for Pipelines to Validate Circulating Biomarkers for Breast Cancer
Karen Anderson, M.D., Ph.D., Associate Professor, School of Life Sciences, Biodesign Institute, Arizona State University
There has been significant progress in the discovery of potential circulating biomarkers, including proteins, autoantibodies, nucleic acids, exosomes, and circulating tumor cells, but the vast majority of these biomarkers have not progressed beyond initial research discovery, and none have yet been approved for clinical use in early stage disease. We will review the crucial considerations of developing pipelines for the rapid evaluation of circulating biomarkers for breast cancer.
2:35 Germline Findings in Tumor-Only Sequencing
Victoria M. Raymond, Adjunct Clinical Assistant Professor, Licensed Certified Genetic Counselor, Cancer Genetics Clinic, University of Michigan Health System
Precision oncology holds great potential to improve patient outcomes. Tumor sequencing is rapidly moving into clinical care as our understanding of the cancer genome and the availability of targeted therapies increase. Analysis of the cancer genome is most informative when paired with germline DNA to delineate inherited and somatic variants. Although tumor-only analysis remains the most common methodology, it holds the potential to identify clinically significant germline variants.
3:05 Refreshment Break
3:35 PANEL DISCUSSION: Clinical Utility and Cost Effectiveness of Predictive Cancer Biomarkers
Moderator: Michael J. Heller, Ph.D., Professor, Bioengineering & Nanoengineering, University of California San Diego
Panelists: David Hoon, Ph.D., Director of the John Wayne Cancer Institute
Raj Krishnan, Ph.D., CEO, Biological Dynamics
Christos Hatzis, PhD, Assistant Professor, Medicine; Director, Bioinformatics, Breast Medical Oncology, Yale Comprehensive Cancer Center, Yale School of Medicine
Among other things, the use of a cancer biomarker is determined by its predictive value and any cost saving that enables a physician to better determine treatment, to modify or change treatment and which increases the likelihood of patient survival. Information that allows switching the patient from an expensive, ineffective, or toxic therapy earlier or faster will be most beneficial. On the other side of the equation is the intrinsic cost of the assay or technology required to detect and analyze the biomarker(s). Improvements in this area will allow better cost to benefit ratios, and lead to more widespread use of the biomarker in cancer diagnostics.
4:35 Close of Symposium