Circulating nucleic acids allow for the possibility of early, non-invasive detection of cancers. They also represent a highly sensitive biomarker of metastatic disease and are capable of reflecting tumor burden and dynamics. Cambridge Healthtech Institute's Inaugural Circulating Cell-Free Nucleic Acids will showcase clinical, technical, and biological aspects of ctDNA, cfDNA and cfRNA. Molecular counting technologies, including digital PCR and next-generation sequencing, will be evaluated and new technologies and techniques will be showcased. Special focus will be given to clinical case studies to further explore the applications and potential of circulating cell-free DNA in cancer diagnostics.

Final Agenda

WEDNESDAY, 15 APRIL

CIRCULATING TUMOR DNA (ctDNA) IN LIQUID BIOPSY

13:00 Chairperson’s Opening Remarks

Catherine Alix- Panabières, Ph.D., Director, Laboratory Rare Human Circulating Cells, Cell and Tissue Biopathology of Tumors, University Medical Center of Montpellier, France

13:35 Real-Time Liquid Biopsy in Cancer Patients: Circulating Tumor Cells vs. Circulating Tumor DNA

Klaus Pantel, M.D., Professor and Founding Director, Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, University of Hamburg, Germany

The analysis of therapeutic targets and drug resistance–conferring gene mutations on circulating tumor cells (CTCs) and cell-free circulating tumor DNA (ctDNA) released into the peripheral blood is now feasible. Both CTCs and ctDNA provide complementary information on assessing new drugs or drug combinations. The liquid biopsy concept will contribute to a better understanding and clinical management of drug resistance in patients with cancer.

14:05 Detection and Characterization of Viable Circulating Tumor Cells as Liquid Biopsy for Cancer

Catherine Alix- Panabières, Ph.D., Director, Laboratory Rare Human Circulating Cells, Cell and Tissue Biopathology of Tumors, University Medical Center of Montpellier, France

The enumeration and characterization of circulating tumor cells (CTCs) in the peripheral blood may provide important prognostic information and might help to monitor efficacy of therapy. Since current assays cannot distinguish between apoptotic and viable CTCs, it is now possible to apply the fluoroEPISPOT assay that detects proteins secreted/released/shed from single epithelial cancer cells. We applied this technology in breast, colon, prostate, head & neck and ovarian cancer as well in melanoma.

14:35 Circulating Tumor DNA for Noninvasive Cancer Diagnostics

Dana W.Y. Tsui, Ph.D., Postdoctoral Research Fellow, Cancer Research UK Cambridge Institute, United Kingdom

This talk will discuss recent advances in the use of circulating tumor DNA for non-invasive study of cancer genomics, with particular focus on non-small cell lung cancer. Clinical cases will be presented to demonstrate its potential clinical utility for molecular stratification, monitoring disease progression and detecting acquire resistance to therapies.

15:05 Refreshment Break in the Exhibit Hall with Poster Viewing

15:45 Blood-Based Genotyping of Colorectal Cancer Patients

Giulia Siravegna, Oncology, University of Torino; IRCC-Candiolo Cancer Institute, Italy

Liquid biopsy and cfDNA analysis allow genotyping of colorectal cancer (CRC) patients using a blood sample. CRC patients represent a model to assess whether blood analyses could in principle be used to perform diagnosis, to guide clinical decisions and to monitor the efficacy of therapies, establishing proof of principle that genotyping of cancer alleles in the patients’ blood allows clinically valuable longitudinal assessment for patients.

16:15 ctDNA in Triple Negative Breast Cancer Patients in a Targeted Therapy Multicentric Clinical Trial

Jean-Yves Pierga, Ph.D., Professor, Medical Oncology, Circulating Biomarkers Lab, Institut Curie & Université Paris Descartes, France

16:45 Networking Reception in the Exhibit Hall with Poster Viewing

17:45 Close of Day

THURSDAY, 16 April

8:00 Registration

8:30 Breakfast Presentation (Sponsorship Opportunity Available)
or Morning Coffee

Circulating Tumor DNA for Patient Management

9:00 Chairperson’s Remarks

Klaus Pantel, M.D., Professor and Founding Director, Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, University of Hamburg, Germany

9:05 Circulating Cell-Free DNA as a Strong Multimarker Diagnostic, Theranostic and Prognostic Tool for Metastatic Colorectal Cancer Patients Management Care

Alain R. Thierry, Ph.D., Senior Investigator, Institute of Research on Oncology of Montpellier, INSERM, France

Circulating cell-free DNA (ccfDNA) appears as a liquid biopsy and a breakthrough tool in cancer diagnostics. We designed a test enabling multimarker ccfDNA analysis. We recently presented first clinical validation of the analysis of circulating DNA in oncology. Potential of examining qualitative (mutational status) and quantitative (concentration of ccfDNA various species) is investigated in regards to diagnostics, prognosis and patients follow up.

9:35 Picoliter Droplet-Based Digital PCR for the Quantitative Analysis of Circulating Tumor DNA for Cancer Patient Follow Up

Valerie Taly, Ph.D., Group Leader, UMR S1147, University of Paris Descartes, CNRS, France

Picoliter droplet-based digital PCR represents a highly efficient tool for cancer research, allowing unprecedented sensitivity and accuracy for rare sequences detection. We will illustrate its pertinence for overcoming actual clinical oncology challenges by presenting the results of different retrospective and prospective studies. In particular, the detection of circulating tumor DNA and its potential use for patient treatment management will be demonstrated.

10:05 Quantification of Circulating Biomarkers from Plasma and Serum Using AC Electrokinetics

David J. Charlot, Ph.D., President and CTO, Biological Dynamics, Inc.

Interest in the isolation, quantification, and analysis of cell-free biomarkers directly from blood has grown significantly. Biological Dynamics has developed proprietary platforms for isolating and quantifying large circulating biomarkers from physiological solutions using AC Electrokinetics (ACE). Biomarkers, such as necrotic cell-free DNA (ncfDNA), have been established as indicators of cancer, and the ability to detect and track these biomarkers unlocks a new era in early disease diagnosis and treatment response monitoring.

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

13:15 Session Break

Technology to Capture and Characterize

14:15 Chairperson’s Remarks

Fred R. Kramer, Ph.D., Professor, Microbiology, Biochemistry & Molecular Genetics, Rutgers University, United States

14:20 Multiplex Detection of Extremely Rare Mutant Sequences Associated with Cancer

Fred R. Kramer, Ph.D., Rutgers University, United States

Extraordinarily specific “SuperSelective” PCR primers enable the simultaneous quantitation of extremely rare mutations that occur in different cells, even though they are located within the same or adjacent codons. Consequently, multiplex assays for the early detection of mutations associated with cancer should enable therapy to be guided by the results of periodic “liquid biopsies” that analyze DNA fragments present in plasma samples.

15:20 cfDNA Profiling in Large Human Melanoma Blood and Tissue Bank

William A. Robinson, Ph.D., M.D., Rella and Monroe Rifkin Endowed Chair & Professor, Medical Oncology, University of Colorado Denver, Anschutz Medical Campus, United States

We have examined serum and plasma samples for mutated cfDNA in a large number of human melanoma samples and correlated the findings with staging, clinical course and response to various treatment(s). This includes serial samples from individual patients. Our data suggests that patients can be monitored for recurrence and response to treatment using cfDNA.

15:50 LiquidBiopsy™ Platform: A Molecular Platform that Supports Next-Generation Sequence Analysis of Circulating Tumor Cells and Circulating Tumor DNA

Paul W. Dempsey, Ph.D., CSO, Cynvenio Biosystems

Circulating tumor cells (CTC) and cell-free DNA (cfDNA) represent important and distinct templates that can support the analysis of tumor-associated mutations by next generation sequencing (NGS). The two templates present distinct advantages for clinical research analysis and provide complementary information from a blood sample. Support for molecular analysis of CTC and cfDNA requires technology to overcome both limiting template and very high signal to noise ratios. Data will be presented describing how the LiquidBiopsy™ Platform supports analysis of CTC and cfDNA from a blood sample by pairing novel CTC enrichment technologies with high sensitivity sequencing in a single Ion PGM™ System based analysis.

16:20 Refreshment Break in the Exhibit Hall with Poster Viewing

17:00 Single-Tube Enrichment of Mutations in Cancer Gene Panels from Circulating DNA, Using COLD-PCR Prior to Targeted Amplicon Re-Sequencing

G. Mike Makrigiorgos, Ph.D., Professor, Radiation Oncology, Dana Farber and Harvard Medical School, United States

We present a newly developed method via which mutations in numerous amplicons are first enriched via COLD-PCR in a single-tube reaction, prior to targeted re-sequencing. Using this approach, mutations of 0.01-0.1% abundance can be detected via next-generation sequencing.

17:30 From Serum to Saliva Diagnostics – Comparative Studies on Circulating Free Nucleic Acids

Christa Noehammer, Ph.D., Senior Scientist, Molecular Diagnostics, AIT Austrian Institute of Technology, Austria

The aim of our research activities at AIT is to define reliable biomarkers suitable for early and non-invasive disease diagnosis and prognosis. We have particularly focused on the establishment and optimization of a whole range of high throughput technologies (e.g. planar -and bead microarrays, microfluidic quantitative PCR, Luminex bead technology) to meet the special demands and challenges of diagnostic biomarker discovery - and validation in body fluids. Using this specific technology expertise e.g. we successfully discovered autoantibody- and DNA methylation -based diagnostic marker panels for the big 4 cancer entities (breast, colon, prostate, lung) in serum or plasma. Based on these success stories and the evident advantages of saliva as a diagnostic matrix our special interest was now to go for saliva diagnostics and to evaluate saliva among others for its suitability for circulating cell-free nucleic acid-based diagnostics by comparing the reliability and performance of a DNA-methylation and microRNA biomarkers in serum and saliva of breast cancer patients.

18:00 Close of Conference