Cambridge Healthtech Institute’s 5th Annual

Clinical Applications of Circulating Biomarkers

An Era of Biomarker Combination

8-9 May 2019

 

Circulating biomarker testing, including cell-free DNA (cfDNA) and circulating tumor cells (CTCs), are proving to be a pioneering technology that meets the clinical need of non-invasiveness and ease of use. The technologies have been maturing rapidly and are continuing to be improved for better sensitivity and specificity. However, experts in the field are still working to implement these technologies in clinical settings and gain biological insights of these biomarkers. Cambridge Healthtech Institute’s 5 th Annual Clinical Applications of Circulating Biomarkers will focus on emerging clinical applications of cfDNA and CTCs, such as early detection, longitudinal monitoring of disease progression, assessment of treatment response, and prognosis following curative-intent therapy. We will extend the discussion on the use of other blood biomarkers such as RNAs, exosomes, platelets, methylation patterns and epigenomic biomarkers along with many non-oncology applications.

Final Agenda

WEDNESDAY 8 MAY

PLENARY SESSION

11:35 Moderator’s Remarks

Charlotte Ryckman, Associate, Covington & Burling LLP, Belgium

11:45 Precision Diagnostics in Oncology: Expanding Roles of Liquid Biopsies

Nitzan Rosenfeld, PhD, Senior Group Leader, Cancer Research UK Cambridge Institute, University of Cambridge; CSO, Inivata Ltd., United Kingdom

Effective clinical management relies on accurate diagnostic information, which requires effective techniques and the right samples. Next generation sequencing can provide a wealth of information, but implementing innovative technologies into clinical routine can be a challenge. We’ll examine how analysis of cell-free DNA can provide an opportunity to re-examine many of the current clinical decision points, and a test case for adoption of new diagnostic tools.

12:15 Legal and Regulatory Developments in Precision Medicine and Diagnostic Devices

Erik Vollebregt, Partner, Axon Lawyers, The Netherlands

  • What changes will be brought about by the IVDR?
  • What is the impact of the GDPR in the field of precision medicine and diagnostic devices?
  • What are the practical implications of implementation of new European regulations?
  • What are the consequences of the interplay of the IVDR and the GDPR?


12:45
PANEL DISCUSSION: Challenges and Opportunities in European Diagnostic Investments

Moderator:

Philippe Peltier, Partner, Kurma Partners, France






Panelists:

Florian Kainzinger, PhD, Managing Partner, Founder, Think.Health Ventures, Germany





Makinen_SeppoSeppo Mäkinen, Partner, Pathena Investments


  • What is different in Europe versus other markets (e.g., US and Israel). How do different European markets compare?
  • What has changed in the landscape of European investments over the past few years? What can be improved?
  • The role of regulators and governments
  • How can start-ups stand out and get attention in the current landscape?

CLINICAL VALUES OF CTCs AND cfDNA

14:30 Chairperson's Remarks

Daniel Wetterskog, PhD, Senior Scientist, Treatment Resistance Team, Oncology University College London Cancer Institute, United Kingdom


14:35 KEYNOTE PRESENTATION: Liquid Biopsy: The New Diagnostic Concept in Oncology

Klaus Pantel, MD, Professor, Chairman, Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Germany

Liquid biopsy assays are currently being validated for early detection of cancer, which is supposed to reduce cancer related mortality. In patients with diagnosed cancer, CTCs and ctDNA analyses can obtain independent information on prognosis in early and advanced stages of disease. Another key application of liquid biopsy is to identify therapeutic targets or mechanisms of resistance of metastatic cells in individual patients.

15:05 Cancer Screening with Circulating Tumor DNA Analysis – The Nasopharyngeal Carcinoma Model

Lam_JackyWai Kei Jacky Lam, MBBS (HK), MPhil, FRCSEd, FHKCORL, FHKAM (Otorhinolaryngology), Clinical Lecturer, Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong

Analysis of circulating tumor DNA (ctDNA) has demonstrated promising results for cancer diagnostics. Screening of nasopharyngeal carcinoma (NPC) with plasma Epstein-Barr virus (EBV) DNA, as a form of ctDNA, has shown clinical benefits in terms of early cancer detection and improved survival. Based on the molecular characteristics of plasma EBV DNA, a sequencing-based assay was developed to improve the test performance of the EBV DNA-based screening test. This has shed light on future directions on ctDNA analysis for screening of other types of cancers.

15:35 Next-Generation Biopsies: Blood-Based Prediction of Treatment Resistance in Gastrointestinal Cancers

Valeri_NicolaNicola Valeri, MD, PhD, Reader in Gastrointestinal Oncology and Consultant Medical Oncologist, The Institute of Cancer Research and The Royal Marsden Hospital, United Kingdom

Liquid biopsies are emerging as rapid and cost-effective tools for the management of cancer patients. I will describe the promises and hurdles of liquid biopsies in deciding and monitoring treatment in patients with advanced metastatic colorectal cancer treated with targeted agents. I will also highlight the potential of combining different biomarkers in liquid and tissue biopsies in order to improve patients’ selection and accelerate precision cancer medicine.

16:05 Refreshment Break in the Exhibit Hall with Poster Viewing

17:05 Cancer-Specific Genetic and Epigenetic Signatures in Plasma DNA from Metastatic Prostate Cancer Patients

Wetterskog_DanielDaniel Wetterskog, PhD, Senior Scientist, Treatment Resistance Team, Oncology University College London Cancer Institute, United Kingdom

Previously, we have shown the association of specific gene aberrations, found in plasma, and the response to currently used therapies in metastatic castration-resistant prostate cancer patients. Currently, we are investigating the correlation of plasma and solid tumour-derived genome wide signatures across the disease setting from diagnosis to end of life. I will present data from our rapid autopsy project where we have gained understanding how ctDNA reflects the genomic and epigenomic landscape of different metastatic lesions. I will also describe our studies in the early disease setting and the PARADIGM clinical trial (Plasma Analysis for Response Assessment and to DIrect the manaGement of Metastatic prostate cancer). In this trial we are investigating the association of plasma derived tumour signatures and the association of outcome in metastatic castration-sensitive prostate cancer patients.

17:35 Towards a Screening Test for Cancer by Circulating Cell-Free DNA Analysis

Thierry_AlainAlain Thierry, PhD, Director, Research, Institut de Recherche en Cancérologie de Montpellier-INSERM, France

Our group has been interested in the implication of cfDNA in the field of oncology for many years, mainly in mutation detection and resistance to treatment, surveillance of recurrence, pre-analytical considerations, as well as cfDNA structure and origins. In addition, we are particularly focused on evaluating its potential for screening and the early detection of cancer. We believe that structural features might help in screening cancer. Therefore, we developed a test (MNR: Multi normalized ratio), based on various cfDNA parameters determined by a specific q-PCR based method, on both nuclear and mitochondrial sequences. The MNR test enables the discrimination between cancerous and healthy individuals (AUC >0.90, 1,500 individuals). In addition, structural observation by whole genome sequencing analysis might also help towards cancer screening.

18:05 Breakout Discussions View Details

19:05 Close of Day

THURSDAY 9 MAY

08:30 Registration and Morning Coffee

UNDERSTANDING THE BIOLOGY OF CTCs AND METASTASIS

09:00 Chairperson's Remarks

Catherine Alix-Panabieres, PhD, Assistant Professor; Director, Laboratory of Rare Human Circulating Cells (LCCRH), University Medical Centre of Montpellier, France

09:05 Biology and Vulnerabilities of Circulating Tumor Cell Clusters

Aceto_NicolaNicola Aceto, PhD, Professor, Oncology, Swiss National Science Foundation, Biomedicine, University of Basel, Switzerland

Cancer patients that develop a metastatic disease are currently considered incurable. Mainly, this is due to a limited understanding of the molecular mechanisms that characterize the metastatic process, and the lack of effective metastasis-suppressing agents. Using a combination of liquid biopsies, microfluidics, single cell sequencing, molecular and computational biology, we are gaining fundamental insights into the biology of circulating tumor cells (CTCs). Further, we have identified FDA-approved agents that target metastatic CTCs and suppress the spread of cancer in preclinical models.

09:35 Molecular and Functional Characterization of Metastasis-Initiator CTCs in Carcinoma Patients

Alix-Panabières_CatherineCatherine Alix-Panabieres, PhD, Assistant Professor; Director, Laboratory of Rare Human Circulating Cells (LCCRH), University Medical Centre of Montpellier, France

Circulating tumor cells (CTCs) are an important clinical indicator for prognosis or treatment efficacy. However, an in-depth investigation of CTCs is hampered by the low number of these cells, making the establishment of permanent cell lines from CTCs very challenging. For the first time, we established and characterized 9 CTC lines obtained from a metastatic colorectal cancer patient before and after systemic therapy (chemotherapy and targeted therapy) and subsequent cancer progression.

BioRad 10:05 Transforming Oncology Research: Droplet Digital™ PCR and his key role in Molecular Profiling of Cancer

Marco Bianchi, Digital Biology EMEA Product Manager, Life Sciences, Bio-Rad Laboratories, Italy

Traditional tissue biopsies limit our ability to implement personalized treatments in disease-associated mutations (i.e cancer). Liquid biopsies can eliminate the need for invasive surgical procedures and now numerous studies have shown that Droplet Digital™ PCR (ddPCR™) enables absolute and highly sensitive quantification using a simple, fast, and economical workflow.

 

10:35 Coffee Break in the Exhibit Hall. Last Chance for Poster Viewing.

11:20 Metabolic Phenotyping and Single-Cell Sequencing of Circulating Tumor Cells in Non-Small Cell Lung Cancer

Shi_QihuiQihui Shi, PhD, Professor, Fudan University, Shanghai Medical College, China

Using a single-cell on-chip metabolic cytometry and fluorescent metabolic probes, we show metabolic phenotyping on the rare disseminated tumor cells in liquid biopsies. Our results reveal extensive metabolic heterogeneity of tumor cells that differentially engage in glycolysis and mitochondrial oxidation. The cell number ratio of the two metabolic phenotypes is found to be predictive for the patient therapy response, clinical performance and survival.

11:50 New Developments in Diagnostic Leukapheresis for Improved CTC-Analysis

Stoecklein_NikolasNikolas Hendrik Stoecklein, MD, Professor, Experimental Surgical Oncology, Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Düsseldorf, Germany

Diagnostic leukapheresis (DLA) is based on continuous centrifugation collecting mononuclear cells from peripheral blood with a density of around 1.05–1.08 g/mL. Since epithelial cells have a similar density, DLA co-collects circulating tumor cells (CTCs) along with the targeted mononuclear cells. The presentation will provide an update on the use and validation of DLA in different cancer entities. So far, the conclusion is that DLA is a clinically safe method to collect CTCs from liters of blood enabling a real liquid biopsy. Even the processing of 5% the DLA product using the CellSearch system led to a significant increase in CTC numbers and detection frequency when directly compared to a peripheral blood sample. Yet, further technical developments are required to process whole DLA products and exploit the full potential of this approach as powerful CTC pre-enrichment step.

12:20 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

APPLICATIONS OF OTHER BLOOD BIOMARKERS: EXOSOMES AND miRNA

13:50 Chairperson's Remarks

Nikolas Hendrik Stoecklein, MD, Professor, Experimental Surgical Oncology, Department of General, Visceral and Pediatric Surgery, University Hospital and Medical Faculty of the Heinrich-Heine University Düsseldorf, Düsseldorf, Germany

14:00 Liquid Biopsy in Ovarian Cancer: The Potential of Circulating miRNAs and Exosomes

Lianidou_EviEvi Lianidou, PhD, Professor, Analytical Chemistry, Clinical Chemistry, Chemistry, University of Athens, Greece

Circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating cell-free microRNAs (cfmiRNAs) and circulating exosomes represent the major components of liquid biopsy analysis. Liquid biopsy has been already implemented in ovarian cancer, and most studies so far are mainly focused on CTCs and ctDNA. This talk is mainly focused on the clinical potential of circulating miRNAs and exosomes as a source of liquid biopsy biomarkers in ovarian cancer diagnosis, prognosis, and response to treatment.

14:30 Exosomes as Emerging Players in Cancer Biology and Diagnostic Applications

Costa-Silva_BrunoBruno Costa-Silva, PhD, Systems Oncology, Group Leader, Champalimaud Foundation, Portugal

We have shown that exosomal patterns of integrins expression dictates the tissue affinity of tumor exosomes, which in turn determines the location of pre-metastatic niches formation and the tumor metastasis organ distribution. Our clinical data indicate that exosomal integrins could be used to predict organ-specific metastasis, helping to answer one of the greatest unsolved mysteries of metastatic cancer regarding the biological basis of organotropism.

NON-ONCOLOGY APPLICATIONS: BRAIN INJURY AND TRANSPLANTATION

15:00 Chairperson's Remarks

Andrea Regner, MD, PhD, Professor, Cellular and Molecular Biology Applied to Health, Course of Medicine, Lutheran University of Brazil, Canoas, Brazil

15:00 The Value of Measuring cfDNA Concentration by a Rapid Florescent Assay in Emergency Medicine  

Douvdevani_AmosAmos Douvdevani, PhD, professor of Biochemistry, Department of Clinical Biochemistry and Pharmacology,  Soroka Medical Center and Ben-Gurion University of the Negev, Israel 

We have developed a fast "Mix and Measure" fluorometric assay to measure cfDNA concentration in biological fluids that has the potential to become a routine clinical test. In my talk, I will demonstrate the advantage of this rapid fluorescent assay over standard clinical scores used in emergency medicine, namely, APACHE II, Ranson, and other multifactorial complex scores. For example, studies on septic, TBI, pancreatitis and smoke inhalation injury patients. 

15:30 Prognostic Utility of Cell-Free DNA in Acute Brain Injuries

REGNER_AndreaAndrea Regner, MD, PhD, Professor, Cellular and Molecular Biology Applied to Health, Course of Medicine, Lutheran University of Brazil, Canoas, Brazil

In acute brain injuries cfDNA has shown to be a promising biomarker for risk stratification, prognosis prediction, monitorization of lesion progression and of therapeutic response, as well as a tool for analysis of the quality of care. We will discuss (i) the prognostic utility of cfDNA in acute brain injuries, particularly traumatic brain injury and brain death; and (ii) the potential of cfDNA as a point-of-care marker in emergency and critical care settings.

16:00 Stroke and Brain Damage Blood Biomarkers

Montaner_JoanJoan Montaner, PhD, Laboratorio de Investigación Neurovascular, Vall d'Hebron Institute of Research (VHIR), Hospital Vall d'Hebron, Barcelona, Spain

The inflammatory response triggered after the ischemic event plays an important role in the progression of stroke; consequently, the study of inflammatory molecules in the acute phase of stroke has attracted increasing interest in recent decades. This talk will discuss the inflammatory processes occurring during ischemic stroke, as well as the potential for these inflammatory molecules to become stroke biomarkers and the possibility that these candidates will become interesting neuroprotective therapeutic targets to be blocked or stimulated in order to modulate inflammation after stroke.

16:30 Graft-Derived Cell-Free DNA as a Biomarker in Organ Transplantation

Oellerich_MichaelMichael Oellerich, MD, Hon MD, FAACC, FAMM, FFPath (RCPI), FRCPath, Distinguished Research Professor, Clinical Chemistry, Clinical Pharmacology, George-August-University, University Medical Center Goettingen, Germany

Molecular biomarkers have attracted special attention in transplantation because of unresolved problems that limit long-term outcome. A particularly promising new approach for the early detection of graft rejection is based on the determination of graft-derived circulating cell-free DNA (GcfDNA). Independent studies have shown that GcfDNA detects rejection episodes early, at an actionable stage, and is a more reliable marker of graft injury, compared to conventional tests. GcfDNA may also be useful to guide changes in immunosuppression, to monitor immunosuppression minimization (e.g. during tapering), and to prevent immune activation. In summary, this approach will allow more personalized treatment that shifts emphasis from reaction to prevention.

17:00 Close of Conference