|Rational Design, Preclinical Evaluation and Clinical Translation of Novel Multimodal Cancer Therapy Regimens
consisting of novel biologicals and targeted inhibitors of the key
pathways in tumor angiogenesis are tested alone and in combination with
radiation and chemotherapy. Currently the following pathways and
corresponding inhibitors are subject of investigation:
a) Small molecular receptor tyrosine kinase inhibitors of VEGF, PDGF and bFGF signaling
b) TGFbeta signaling (small molecular TGFbeta RI and dual RI+II kinase inhibitors)
c) Integrin signaling (peptide and peptidomimetic antagonists of alpha V and beta 3/5 integrins)
d) Cyclooxygenase (COX-2) inhibitors
e) EGF signaling (antibody against EGFR with direct endothelial effects + indirect downregulation of VEGF, bFGF & IL8)
f) endogenous angiogenesis inhibitors (endostatin and angiostatin)
g) Toll like receptor agonists
The Role of Tumor-Vessel
Interface in Trimodal Cancer Therapy
Priority Research Program of the German Research
Foundation (Deutsche Forschungsgemeinschaft, DFG)
"SPP 1190: The Tumor-Vessel Interface"
|Attenuation of Radiation Induced Normal Tissue Toxicity
|One major focus is to test anti-fibrogenesis effects of PDGF and TGFbeta signaling inhibitors in our well established radiation induced lung fibrosis mice model. Fibrosis is induced ~ 16-20 weeks post radiation and is monitored by non-invasive methods (Volume-CT, MRI) and histology (e.g. Sirius, trichrom staining). This model is now used to determine heavy ions (carbon beams) induced lung toxicity. In frame work of new heavy ions facility in Heidelberg (HIT), colon- and neurotoxicity of C12 radiation is further investigated.
|The Molecular Mechanisms of
Action and Relative Biological Effectiveness (RBE) of Carbon Beams
Radiation vs. Photons
In preparation for the new Heidelberger Ionenstrahl Therapiezentrum (HIT) facility the RBE of tumor and microenvironmental cells are determined in-vitro and in syngenic rat prostate cancer model in-vivo. In analogy to our work on systemic investigation of photon irradiation, the molecular and pathophysiological features of C12 therapy will be characterized.
|The Molecular Mechanisms of Tumor Dormancy and Tumor Angiogenic Switch
|a) development of
strategies to systematically dissect the genetic participants and
regulatory networks involved in the angiogenic switch process.
b) Deciphering the molecular mechanism of tumor dormancy and angiogenic switch in animal tumor models established, i.e., dormant vs. fast growing human breast cancer, osteosarcoma, liposarcoma and glioblastoma models.
|Solid tumor risk estimation:
incorporating intercellular interaction effects
NASA Specialized Center of Research (NSCOR)
The NSCOR will provide a composite space radiation carcinogenesis model designed to reduce the uncertainties in risk estimates for astronauts.
Role of Endothelial Cell Apoptosis in Tumor Response to Radiotherapy"
Research Program of the German Krebshilfe
"Apoptosis deficiency and its modulation in malignant disease"
|Immunosuppresive Drugs and Cancer
anti-tumor activity (i.e., anti-angiogenic and anti-fibrotic effects) of
novel targeted immunosuppressive agents used in transplantation medicine.
Currently, mTOR, IMPDH, PKC, S1P and JAK3 pathways are investigated.
In collaboration with Sophie Domhan, Nephrology department, University of Heidelberg Medical School
|Systematic Transcriptional Characterization of Pancreatic Cancer
|In collaboration with
Helmut Friess, Joerg Kleeff
and Irene Esposito, Surgery and Pathology
departments, university hopspitals of TU Munich (TUM), we
systematically investigate the transcriptome of pancreatic cancer.
Currently, more than 300 specimens from patients undergoing surgery (with
and without prior "neoadjuvant" therapy) have been profiled with our
whole human genome cDNA microarray platform in combination with high
density tissue microarrays. Following topics are subject of
a) the role of tumor microenvironment in development of pancreatic cancer in patients with chronic pancreatitis
b) molecular determinants of tumor differentiation (G1 vs. G3 tumors)
c) molecular determinants of tumor lymph node metastasis (N0 vs. N+ tumors)
d) effects of neodjuvant radiotherapy + gemcitabine (gemzar) vs. intensity modulated radiotherapy (IMRT) + gemzar vs. IMRT+ Cetuximab (PARC trial)
e) Investigation of primary tumors vs. lymphnode or liver metastasis
|Whole Blood Expression Profiling to Predict Therapy Response
|Currently, we investigate
this method to predict therapy response in:
a) Patients with arteriovenous malformation after Stereotatic Radiosurgery
b) Patients with locally advanced pancreatic cancer (PARC) treated with trimodal cancer therapy consisting of radiotherapy, chemotherapy and EGFR-inhibition (Cetuximab)
c) Patients with acute kidney injury (AKI) post cardio-pulmonary bypass operation. In collaboration with Orfeas Liangos and Bertrand Jaber, Nephrology department, Caritas St. Elizabeth's medical center, Boston.