Pruschy Martin

Group Leader

Prof. Dr. Martin Pruschy

 

Name of the Institution

Laboratory for Molecular Radiobiology
Department of Radiation Oncology
University Hospital Zürich

Street

Rämistrasse 100

City

CH-8091 Zürich

Phone

+41-44-255 85 49
+41-44-255 29 30

E-mail

Group Members

Furmanova, Polina, PhD student: polina.furmanova@usz.ch
Hollenstein, Andreas, PhD student: andreas.hollenstein@usz.ch
Millard, Anne-Laure, PhD, anne-laure.millard@usz.ch
Oehler, Christoph, MD: christoph.oehler@usz.ch
Rohrer Bley, Carla, vetMD: crohrer@vetclinics.uzh.ch
Vuong, Van, Technician: van.vuong@usz.ch
Wergin, Melanie, vetMD: melanie.wergin@vetclinics.uzh.ch

Main Field(s) of Research, Abstract

The major focus of our translational research activities is 'Combined Treatment Modality in Radiation Oncology'. This program consist of 3 major topics that investigate the tumor cell and tumor response to ionizing radiation alone and in combination with classic chemotherapeutical or novel pharmacological anticancer agents. A major goal is to understand treatment resistance of human solid malignancies on the molecular, cellular and in vivo level and to translate novel combined treatment modalities into a clinical setting.
1. Ionizing Radiation-Induced Intracellular Signaling: Relevance for Radiation Resistance: We investigate ionizing radiation-induced signaling processes in tumor cells and endothelial cells with two approaches -With classical biochemical and cell biology tools irradiation-activated signal transduction cascades and their contribution to the cellular radiosensitivity profile are analyzed. -With a substractive Substrate Peptide Phage Display Library approach treatment-specific and cell type specific (transformed vs non-transformed) enzymatic activities are identified and putative substrate/inhibitor-peptide-sequences are developed.
2. Identification of Novel and Clinically Relevant Pharmacological Compounds for Combined Treatment with Ionizing Radiation (e.g. potential radiosensitizers): In close collaboration with Novartis Pharma, we investigate the radiosensitizing potential of chemotherapeutical compounds that are part of the R&D program of Novartis. In particular we focus on (proto-)oncogene kinase inhibitors, kinase inhibitors of the growth factor receptor family, cyclooxygenase-inhibitors etc. and test their radiosensitizing effect in vitro and in vivo followed by mechanistic studies on the mechanism of radiosensitization on the cellular and molecular level.
3. Inhibition of Angiogenesis in Combination with Ionizing Radiation: This novel and promising combined treatment modality is investigated in murine spontaneous and allograft/xenograft tumor models to understand the influence of the angiogenic microenvironment and treatment sequence of this treatment strategy. Mechanistic and cellular studies investigate the role of the PI3K/Akt-pathway in endothelial cells and its contribution to the tumor growth control effect of this combined treatment modality

Main Fields of Research, Keywords

Ionizing radiation, mechanism and efficacy of novel radiosensitizers, radiochemotherapy, angiogenesis, apoptosis, signal transduction, p53, PI3K/Akt, peptide phage display, xenograft and spontaneous mouse tumor models

Special Techniques and Equipment

Irradiation with ionising radiation, site-directed mouse irradiation, clonogenic assay, peptide phage display

Education and Training

We have training opportunities for PhD- and MD- students and MDs interested in the research topics mentioned above For MD Thesis: minimal duration of MD Thesis in the Laboratory is 6 -12 months

Selected Publications

Oliver Riesterer, Michael Honer, Wolfram Jochum, Christoph Oehler, Simon Ametamey and Martin Pruschy (2006) Ionizing radiation antagonizes tumor hypoxia induced by anti-angiogenic treatment Clinical Cancer Research, 12, 3518-3524

Barbara Hofstetter, Van Vuong, Angela Broggini-Tenzer, Stephan Bodis, Ilja F. Ciernik, Doriano Fabbro, Markus Wartmann, Gerd Folkers and Martin Pruschy (2005). Patupilone (EPO906) Acts as Radiosensitizing Agent in Multidrug-Resistant Cancer Cells in Vitro and in Vivo. Clinical Cancer Research, 11, 1588-1596

Daniel Zingg, Oliver Riesterer, Christoph Glanzmann, Stephan Bodis and Martin Pruschy (2004). Differential Activation of the PI3K/Akt-Survival Pathway by Ionizing Radiation in Tumor and Primary Endothelial Cells. Cancer Research, 64, 5398-5406

Angela Tenzer, Barbara Hofstetter, Christelle Sauser, Stephan Bodis, Christophe Bonny and Martin Pruschy (2004). Profiling treatment-specific posttranslational modifications in a complex proteome.Proteomics, 4, 2796-2804

Riesterer O, Hummerjohann J, Bodis S, Pruschy M (2004). Degradation of PKB/Akt Protein by Inhibition of the VEGF-Receptor and the mTOR Pathway in Endothelial Cells. Oncogene, 23, 4624-4635

Tenzer A and Pruschy M (2003). Potentiation of DNA-Damage-Induced Cytotoxicity by G2 Checkpoint Abrogators. Current Medicinal Chemistry - Anti-Cancer Agents, 3, 35-46

Tenzer A, Zingg D, Riesterer O, Vuong V, Bodis S, and Pruschy M (2002) Signal Transduction Inhibitors as Radiosensitizers. Current Medicinal Chemistry - Anti-Cancer Agents, 2, 727-742

Tenzer A, Zingg D, Rocha S, Fabbro F, Glanzmann C, Schubiger PA, Bodis S, and Pruschy M (2001). The PI3K/Akt Survival Pathway is a target for the Anticancer and Radiosensitizing Agent PKC412, an inhibitor of Protein kinase C. Cancer Research, 61, 8203-8210

Zaugg K, Rocha S, Resch H, Hegyi I, Oehler C, Glanzmann C, Fabbro F, Bodis S, and Pruschy M (2001). Differential, p53-dependent Mechanism of Radiosensitization in vitro and in vivo by the cPKC-specific Inhibitor PKC412. Cancer Research, 61, 732-738

Hess C, Vuong V, Hegyi H, Riesterer O, Wood J, Fabbro D, Glanzmann C, Bodis S, and Pruschy M (2001). The Effect of the VEGF Receptor Inhibitor PTK787/ZK222548 combined with Ionising Radiation on Endothelial Cells and Tumour Growth. Brit. J. of Cancer, 85, 2010-2016

Funding

Swiss National Foundaqtions, Swiss Cancer League, Zurich Cancer League, Novartis Pharma

URL

Under construction

Link to "Forschungsdatenbank" of the University

To be updated