Innovation Field Explorer, Merck KGaA, Germany
Discover how experts are utilizing technologies such as qPCR, digital PCR and NGS to accelerate the development of liquid biopsies into a leading non-invasive diagnostic test for cancer. Talks focus on circulating biomarkers such as cell-free DNA, (cfDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs).
“I met leading companies/biomarker developers at one place sharing cutting edge technologies”.
“Interesting mixture of topics; possibility to discuss with the attendees”
“Learned a lot from some of the talks”
THURSDAY 10TH OCTOBER 2019 – LIQUID BIOPSIES; TECHNIQUES AND TECHNOLOGIES
Keynote Address: A universal biomarker for cancer: Are we there yet?
MATT TRAU, Professor of Chemistry, Deputy Director and Co-Founder of AIBN, University of Queensland, Australia
Epigenetic reprogramming in cancer genomes creates a distinct methylation landscape encompassing clustered methylation at regulatory regions separated by large intergenic tracks of hypomethylated regions. This methylation landscape that we referred to as Methylscape is displayed by most cancer types, thus may serve as a universal cancer biomarker. We examine the effect of levels and genomic distribution of methylcytosines on the physicochemical properties of DNA to detect the Methylscape biomarker. We find that DNA polymeric behaviour is strongly affected by differential patterning of methylcytosine, leading to fundamental differences in DNA solvation and DNA-gold affinity between cancerous and normal genomes. We exploit these Methylscape differences to develop simple, highly sensitive and selective electrochemical or colorimetric one-step assays for the detection of cancer. These assays are quick, i.e., analysis time≤10minutes, and require minimal sample preparation and small DNA input from either solid or liquid biopsies.
Keynote Address: Enabling Liquid Biopsy in Cancer and Beyond
SIMON LUCAS, Innovation Field Explorer, Merck KGaA
The early detection of life-threatening conditions as well as the selection of individualized treatment options for affected patients will have significant potential to disrupt our current public health sectors. Recently, alternatives to traditional tissue biopsy, such as liquid or breath biopsy, have emerged as attractive tools for the detection and management of various diseases and especially in the therapeutic area of oncology. While cancer detection with liquid biopsy is gaining acceptance, other indications often still lack a non-invasive diagnostic test, even though precision medicine is viewed as an important concept in indications outside oncology. This talk highlights the opportunities of liquid biopsy in cancer and beyond as well as our efforts at Merck to address challenges in the field with new enabling technologies.
Morning Refreshments / Poster Presentations / One-to-One Meetings
Considerations when analyzing cell-free tumor DNA
ANDERS STAHLBERG, Associate Professor, University of Gothenburg, Sweden
• Analysis of circulating cell-free tumor DNA (ctDNA) in liquid biopsies offers new means for early cancer diagnostics, real-time monitoring of treatment efficiency and detection of relapse. Despite its potential use ctDNA remains challenging to detect and to quantify as it represents only a small fraction of all cell-free DNA.
• We have developed SiMSen-Seq, that allows allele frequencies < 0.1% to be detected. SiMSen-Seq is simple to perform, flexible in multiplexing and requires minimal DNA input.
• Here, we discuss important considerations for ctDNA analysis in plasma, including all experimental steps from sampling to data interpretation. Furthermore, the use of quality control assays enables the development of robust and standardized workflows that facilitate the implementation of ctDNA analysis into clinical routine.
Standardized analysis of extracellcular vesicles in liquid biopsies
AN HENDRIX, Assistant Professor, University of Ghent, Belgium
The identification of extracellular vesicle (EV)-associated biomarkers is challenging owing to the complexity of liquid biopsies. We 1) performed quality control studies to identify the impact of (pre-) analytical variables on biomarker identification, 2) developed reference materials to ensure standardized EV measurements, and 3) created EV-TRACK to stimulate researchers to put experimental guidelines into practice. This combined expertise boosted the identification of bacterial EV in the systemic circulation of patients with intestinal barrier dysfunction.
Innovation in Research: From Protein Array to Companion Diagnostics to Profiling of Adverse Events
DOLORES CAHILL, Professor of Translational Science, University College Dublin, Ireland
Overview of profiling the autoantibody repertoire on high content protein arrays and using this approach to identify biomarkers, and develop diagnostics and companion diagnostics.
Clinical utility of CTC and ctDNA in metastatic and neo/adjuvant setting of breast cancer
JEAN-YVES PIERGA, Institut Curie, Department of Medical Oncology and Circulating Tumor Biomarkers Laboratory, SiRIC, Université Paris Descartes, France
Circulating tumor cells (CTCs) have been identified as potential blood-based biomarker capable of providing prognostic and predictive information in breast cancer. Their applications include early diagnosis, prognostic assessment, detection of minimal residual disease, early detection of cancer relapse and management of metastatic disease. The clinical validity of the CTCbased liquid biopsy has been already assessed by numerous studies. Pooled analysis of large clinical data set in adjuvant, neoadjuvant and metastatic setting are now available. Recent results of clinical trial could support their clinical utility. The potential applications for circulating tumour DNA (ctDNA) in early and metastatic setting include prognosis assessment before treatment initiation, early assessment of treatment efficacy and help to guide personalized therapies.
ROBERT NEELY (Reserved), Associate Director, Pharmacodiagnostics, BMS
Afternoon Refreshments / Poster Presentations / One-to-One Meetings
Translating liquid biopsies into routine care
PANEL DISCUSSION – Speakers include:
Commercial Partnerships Manager, Genomics England, UK
Innovation Lead – Precision Medicine, Innovate UK
Assistant Professor, Molecular Biologist, Institut de Cancérologie de Lorraine, France
Senior Scientist, AstraZeneca, UK
Head Cellular and Molecular Diagnostics, Division Personalized Tumor Therapy, Fraunhofer-Institute for
Toxicology and Experimental Medicine ITEM-R, Germany
Innovation Field Explorer, Merck KGaA, Germany
Networking Drinks Reception
FRIDAY 11TH OCTOBER 2019 – CLINICAL APPLICATIONS
Keynote Address: A Liquid Biopsy Assay to detect Cancer
DIANA ANDERSON, Established Chair, Biomedical Sciences, University of Bradford, UK
There appeared to be no single test to identify cancer in general, but we have developed such an assay. In this modified patented Comet assay, we investigated peripheral lymphocytes from blood of 208 individuals, known as the Lymphocyte Genome Sensitivity (LGS) test. Ninety four individuals were controls. All cancers tested exhibited comparable responses. Analyses of Receiver Operating Characteristic (ROC) curves, of mean log Olive tail moments for cancer alone versus controls alone, the area under the curve was 0.93. By varying the threshold for test positivity, its sensitivity or specificity can approach 100% whilst maintaining acceptable
complementary measures. Since lymphocytes in blood only are examined, and the test has been repeated with over 900 individuals with equally valid responses, this is a useful Liquid Biopsy assay.
Liquid biopsies on the road to clinical utility
RALPH GRAESER, Senior Translational Medicine Expert, Boehringer Ingelheim
• Use of liquid biopsies in the clinic: diagnostic, prognostic, predictive?
• CTCs vs ctDNA: one or the other – or both?
• CANCER-id – a public-private partnership with the goal to standardize liquid biopsy protocols for clinical use
Morning Refreshments / Poster Presentations / One-to-One Meetings
Novel digital PCR and mutation enrichment technologies for the analysis of clinically relevant DNA alterations in liquid biopsies
MIKE MAKRIGIORGOS, Professor of Radiation Oncology, Dana Farber Cancer Institute and Harvard Medical School, USA
With the increasing interest in treatment assessment using liquid biopsy and circulating DNA, sensitive and multiplexed detection of tumor-derived alterations in blood are desirable. We provide novel forms of digital PCR, as well as mutation enrichment-based real time PCR methods that (a) enable several orders of magnitude improvement of detecting mutations or microsatellite instability than currently possible; (b) are highly multiplex-able; (c) reduce cost of analysis. Application in circulating DNA from clinical cancer samples will be presented.
A targeted multi-analyte liquid biopsy to identify early stage gynecologic cancers
JOHN MARTIGNETTIProfessor, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, and Director, Laboratory of Translational Research, Western Connecticut Health Network, USA
Overwhelmingly the power and success of “liquid biopsy” has been focused on issues related to advanced disease in already diagnosed patients under active treatment. We demonstrate an approach and the feasibility of using a targeted liquid biopsy approach for detecting early stage gynecologic cancers by combining analysis of both DNA and proteins.
CTC analysis: Latest advancements and clinical applications
EVI LIANIDOU, Professor of Analytical Chemistry – Clinical Chemistry, University of Athens, Greece
• Liquid biopsy provides a valuable source of biomarkers through simple and minimally invasive serial blood draws and represents a highly dynamic diagnostic, prognostic and theranostic tool for the management of cancer patients.
• Circulating tumor cells (CTCs) are major players in liquid biopsy and their molecular characterization offers
an exciting approach to monitor the efficacy of systemic therapies in real-time, unravel the biology of cancer cell dissemination, understand resistance to established therapies and identify gene targets and signalling pathways relevant to therapeutic interventions.
• Single-cell CTC analysis is a powerful tool to understand tumor heterogeneity and the mechanisms involved in cancer progression with potential implications for improving treatment strategies.
• This lecture will be focused on the latest developments in the detection and molecular characterization of CTCs, and their clinical applications in many types of cancer.
Prognostic and predictive value of circulating methylated DNA in metastatic colorectal cancer patients treated with regorafenib
LUDOVIC BARAULT, Senior Research Associate, Candiola Cancer Institute and the University of Torino, Italy
• Regorafenib is associated with improved progression free survival (PFS) in a subset of metastatic colorectal cancer
(mCRC) patients and no biomarkers of efficacy are available for this drug which is often associated with many toxicities.
• We previously found an association between circulating methylated DNA and outcome in chemotherapy treated mCRC patients and we hypothesized that such biomarker could be used to identify cases most likely to benefit from regorafenib (i.e. patients with PFS longer than 4 months).
• Assessment of pre and on treatment blood samples confirmed the prognostic value of circulating methylated DNA and suggest its use as biomarker for regorafenib since it may predict unresponsiveness to the treatment.
ANDREAS HAUSER, Staff Scientist, LMU, Germany
Chair’s Closing Remarks / Conference Close
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Poster presentation sessions will take place in breaks and alongside the other breakout sessions of the conference. Your presentation will be displayed in a dedicated area, with the other accepted posters from industry and academic presenters.
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