Diagnostik & Forschungszentrum für Molekulare BioMedizin

Liquid Biopsy


Tumors release components such as of cell-free DNA fragments (ctDNA, circulating tumor DNA) or viable cells (CTC, circulating tumor cells) into the circulation, which reflect their genetic or epigenetic landscape. Therefore, CTC and ctDNA can be used for molecular profiling and prognostication purposes for malignant diseases from blood and other body fluids. A liquid biopsy (LB) refers to the sampling and analysis of non-solid biological tissue, and therefore is a simple and minimal-invasive alternative to surgical biopsies. The LB holds great promise for precision and personalized medicine and in particular, ctDNA has been demonstrated to be a valuable tool to detect cancer recurrence, to predict tumor burden and treatment response, as well as to identify resistance mechanisms and the emergence of novel actionable targets (1-4). However, despite promising data, the analytical validity and clinical utility of ctDNA in plasma have not yet been shown for the vast majority of available ctDNA assays. The potential of ctDNA is not limited to patients already suffering from cancer, it may also play a crucial role in the detection of pre-clinical cancer. To this end, a core understanding of the mechanisms and dynamics underlying ctDNA and the resolution of important technical issues is indispensable. Therefore, very few studies have focused on the evaluation of ctDNA detection in early-stage cancers (i.e. stage I-II tumors) with even less data available on the detection of ctDNA in blood samples from pre-symptomatic cancer patients.

Objectives & ongoing research

At the D&R Institute of Human Genetics at the D&R Centre of Molecular Biomedicine we aim to assess the validity and utility of ctDNA approaches for personalized cancer genomics. Moreover, we intend elucidate the biology and dynamics of ctDNA to eventually bring a broad spectrum of ctDNA approaches to the clinic.

The main objectives of our ongoing projects are:
  • To use ctDNA to monitor treatment response of advanced cancer patients including breast, colorectal, renal and prostate cancer
  • Assessment of ctDNA as a predictive marker for response to immune checkpoint inhibitor in NSCLC
  • Assessment of ctDNA as a predictive marker for response to neo-adjuvant treatment in localized breast cancer
  • Identification of novel driver genes and alterations in genes related to drug resistance based on ctDNA analysis
  • Correlation of ctDNA and tumour size in order to assess the minimal tumour size necessary for ctDNA release
  • Establishment of molecular subtypes from ctDNA using machine learning approaches
  • Generation of a tissue-of-origin maps for plasma DNA healthy and diseased individuals
  • Analysis of nucleosome occupancy patterns in plasma DNA in healthy and diseased individuals
  • Application of multi-parameter approached aided by artificial intelligence 

Our strengths

Extensive experience in the analysis of plasma DNA: Our LB group at the D&F Institute of Human Genetics has extensive experience in the analysis of plasma DNA, which is reflected in numerous publications in high-ranking journals (5-16). We have established a plethora of plasma DNA based approaches to study genome-wide SCNAs and high-sensitivity approaches to detect specific mutations occurring at low allele frequencies.

International recognition: In this highly competitive field, our group is one of the most renowned in the field. Our expertise has been recognized internationally by invitations to international conferences, reviews (1, 3, 17-19), editorials (20, 21) and book chapters (22, 23) in high-ranking international journals.

Multidisciplinary team: Our team consists of physicians, geneticist, molecular biologist, bioinformaticians and pathologists, who are working together on a variety of projects that address multiple challenges in liquid biopsy approached ranging from the development of bioinformatics tools for the analyses of ctDNA to the assessment and clinical interpretations of results generated from these analyses.

Successful acquisition of grant money: In the last years our group leaders (Jochen Geigl, Ellen Heitzer, and Michael Speicher) have been exceptionally successful in the acquisition of research grants including FWF, OeNB, or EU-funded IMI grants. Recently, we were granted the Christian Doppler laboratory “Liquid biopsies for early detection of cancer” with a seven-year budget of 2.08 mio. EUR and two industry partners, i.e. Freenome and PreAnalytiX. The CD lab is a cross-institute project that enables scientific collaboration between globally leading biotech companies in the fields of pre-analytics and molecular diagnostics, and scientists at the Institute of Human Genetics and the Institute of Pathology.

Importance for the D&R Centre of Molecular Biomedicine: Our liquid biopsy efforts fit perfectly into the shared research activities of the D&R Centre of Molecular Biomedicine. First, they involve a close cooperation with the D&R Institute of Pathology, e.g. for the detailed comparison of liquid biopsy results with those obtained from matching tissue biopsies. This long lasting and close collaboration is reflected in numerous joint publications from both the D&R Institute of Pathology and the D&R Institute of Human Genetics. Second, an exciting novel field in the liquid biopsy community is the detection and analyses of pathogens in the circulation. To this end, we have already initiated collaborations with the groups of Prof. Christine Moissl-Eichinger and Prof. Ivo Steinmetz. Hence, the liquid biopsy field supports our efforts in respect to increase synergy and joint research efforts between the institutes of our D&R center.

National collaborations: What distinguishes us from many other LB groups is the close connection to the clinics. We are not only closely collaborating with many clinical departments at our university clinic (Gynecology, Hematology, Oncology, Orthopedics, Urology) but also with other clinical institutions at the AKH Vienna or the Austrian Breast & Colorectal Cancer Study Group (ABCSG), an Austrian organization conducting successful international clinical studies.

International collaborations: Our group is embedded in a network of leading groups in Europe working with liquid biopsies. We are a partner of the Innovative Medicines Initiative (IMI) consortium CANCER-ID which started in January 2015. Furthermore, we are a member of the recently funded European Liquid Biopsy Society (ELBS). It´s main goal is to foster the introduction of liquid biopsy into clinical practice but it is also concerned with encouraging interactions between academia and industry, providing a partner for regulatory agencies, healthcare providers and patient advocacy groups, supporting the implementation of liquid biopsy tests into clinical trials, developing guidelines and providing training in liquid biopsy for medical scientists, disseminating the knowledge about liquid biopsies to the medical community through regular symposia, publications and press release, and more generally, increasing the visibility of Europe as leading hub for liquid biopsy research.

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