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Translational GI oncology, Lab Dr. med. Ralph Fritsch

Our laboratory aims to

  1. Study RAS and PI3 Kinase signalling in order to develop better strategies to target these key oncogenic pathways in patients
  2. Optimize and exploit co-clinical ex vivo organoid modelling for Precision Oncology
  3. Establish novel biomarkers for therapeutic stratification and response monitoring in difficult-to-treat GI cancers

Part of our group is still located at the University of Freiburg (Germany) Hospital Center.

My mission as Head of Medical GI Oncology at USZ is to implement Precision Oncology in all aspects of the clinical management of gastrointestinal and hepato-pancreatico-biliary (HPB) tumors.

Projects

1. Oncogenic RAS and PI3 Kinase (PI3K) Signalling

Our laboratory employs in vitro and in vivo models to study the interplay between small RAS GTPases und PI3K isoforms both on the molecular and translational level. RAS and PI3K lie at the heart of oncogenic signalling and therapeutic targeting of these pathways has remained extremely challenging.

A focus of our laboratory is to integrate next generation patient-derived models into signalling research in order to foster bi-directional translation for Precision Oncology.

Collaboration:

  • Julian Downward, The Crick Institute, London
  • Chantal Pauli, Institute of Pathology and Molecular Pathology, USZ

2. Modeling of GI Cancers with Patient-derived Organoids (PDOs)

Comprehensive molecular profiling fails to identify effective personalized treatment strategies in a large proportion of GI tumors highlighting the need for improved pre- and co-clinical modeling.

Patient-derived cancer organoids (PDOs) uniquely preserve genotype and phenotype of individual tumors and can be studied ex vivo in a co-clinical setting. In an interdisciplinary effort, we have established a large collection of tumor organoids derived from patients undergoing resection or surgical biopsy of pancreatic adenocarcinoma. We study several aspect of tumor biology ex vivo including invasiveness and metastatic behavior and explore individual therapeutic vulnerabilities through combinatorial drug screening.

Key future objectives are to

  • Improve co-clinical organoid modeling (efficiency, representation, complexity, time frame)
  • Expand our efforts to other difficult-to-treat GI tumor entities (BTC, CRC, GEJ/gastric)
  • Validate ex vivo drug testing results in co-clinical organoid trials

Collaboration:

  • Chantal Pauli, Institute of Pathology and Molecular Pathology, USZ
  • Uwe Wittel, Department of Surgery, Freiburg University Hospital
  • Melanie Boerries, Institute of Medical Bioinformatics and Systems Medicine, Freiburg University Hospital
  • Michael Scharl, Department of Gastroenterology and Hepatology, USZ

3. Novel biomarkers for therapeutic stratification and response monitoring

Innovative biomarkers and molecular monitoring hold great potential to personalize multi-modality treatment of GI cancers and better guide systemic therapy. Detection and quantification of tumor-derived cell-free DNA (cfDNA) and the integration of novel protein biomarkers can help better stratify patients and monitor treatment efficacy.

The goal of our laboratory is to establish and integrate innovative liquid biomarkers into the clinical management of GI cancer patients. We employ personalized single- and multi-target digital droplet PCR assays as well as NGS panels and conduct prospective biomarker trials exploring the potential of longitudinal liquid biomarker analysis for personalizing systemic cancer therapy.

Collaboration:

  • Stefan Balabanov, Department of Medical Oncology and Hematology (MOH), USZ
  • Thorsten Zenz, Department of Medical Oncology and Hematology (MOH), USZ
  • Uwe Wittel, Department of Surgery, Freiburg University Hospital
  • Melanie Boerries, Institute of Medical Bioinformatics and Systems Medicine, Freiburg University Hospital
  • Michael Scharl, Department of Gastroenterology and Hepatology, USZ
Publications

Members

Ralph Fritsch, Dr. med.

Oberarzt meV Onkologie, Klinik für Medizinische Onkologie und Hämatologie
Leiter Darmtumorzentrum, Leiter Endokrines und Neuroendokrines Tumorzentrum, stv. Leiter Leber- und Pankreastumorzentrum, stv. Leiter Magen- und Ösophagustumorzentrum, Comprehensive Cancer Center Zürich

Spezialgebiete: Gastrointestinale Tumore, Hepatobiliäre Tumore, Molekulare Onkologie und Präzisionsonkologie
Tel. +41 44 255 22 14

Saskia Hussung

Assistenzärztin Onkologie, Klinik für Medizinische Onkologie und Hämatologie

Tel. +41 44 255 22 14