Priority Research Program of the German Research Foundation (DFG)
SPP 1190 - THE TUMOR - VESSEL INTERFACE

SPP 1190 - Projects
 
A. Abdollahi / P. Huber/
J. Debus

A. Acker-Palmer
T. Acker
R. Adams
F. Alves
H. Augustin
H. Beck / M. Conrad
G. Breier / B. Wielockx
P. Friedl
C. Bruns / P. Nelson
B. Homey / A. Müller-Homey
Ch. Klein
V. Orian-Rousseau / H. Ponta
K.T. Preissner
B. Sipos
J. Sleeman
P. Vajkoczy
 

 

Dr. Amir Abdollahi,
Prof. Dr. P. Huber and
Prof. Dr. J. Debus

 

Molecular RadioOncology [E210]
Heidelberg Ion Therapy Center (HIT)
Department of Radiation Oncology
University of Heidelberg Medical School
Im Neuenheimer Feld 450
&
National Center for Tumor diseases (NCT)
German Cancer Research Center (DKFZ)
Im Neuenheimer Feld 460
69120 Heidelberg
Tel.:++49 (0) 6221-56-39604
Fax.:++49 (0) 6221-56-8537


Lab Homepage

(Dr. Amir Abdollahi)

a.amir(at)dkfz.de

(Prof. Dr. Peter Huber)

p.huber(at)dkfz.de

(Prof. Dr. Jürgen Debus)

j.debus(at)dkfz.de

 
The role of tumor - vessel interface in multimodal cancer therapy
The recognition that antiangiogenic cancer therapy is becoming the fourth therapeutic modality in addition to surgery, chemotherapy and radiotherapy underlines the urgent need to better understand the role of tumor-vessel interface particularly if multimodal therapeutic strategies are attempted. There is now ample of evidence that tumors protect their vasculature from radiation- and chemotherapy induced damage by releasing pro-angiogenic and pro-survival factors. Thus, tumor-vessel communication is emerging as an important target to circumvent chemo- and radio-resistance. Here we propose to systematically characterize the molecular and pathophysiological events that are involved in “tumor-vessel-interaction” in response to endogenous angiogenesis inhibitors and multimodal therapies with emphasis on the emerging problem of acquired tumor resistance to adjuvant antiangiogenic therapy. The key players of tumor resistance to antiangiogenic therapy are identified by genome-wide transcriptional analysis and the promising “targets” will be functionally evaluated for their ability to modulate therapy response by experimental knock out or pharmacological antagonism. We will use these data to rationally design meaningful “antiangiogenic cocktails” and to test for their optimal therapeutic scheduling. We hypothesize that a systematic molecular characterization of “tumor-vessel-resistance” to multimodal therapies (including adjuvant or single antiangiogenic treatment) will navigate preclinical research to the identification of new therapeutic targets. Therefore the proposed research can open a new avenue to improve the design of therapeutic regimen and to develop more powerful clinical protocols.
 
- Relevant recent publications -

Abdollahi A, Folkman J.:Evading tumor evasion: Current concepts and perspectives of anti-angiogenic cancer therapy Drug Resist Updat. Jan 8. [Epub ahead of print], 2010

Zabel-du Bois A, Wagner-Ecker M, Milker-Zabel S, Schwager C, Wirkner U, Debus J, Abdollahi A, Huber PE. :Gene Expression Signatures in the Peripheral Blood After Radiosurgery of Human Cerebral Arteriovenous Malformations. Strahlenther Onkol. Feb;186(2):91-98. Epub 2010 Jan 28, 2010

Behren A, Mühlen S, Acuna Sanhueza GA, Schwager C, Plinkert PK, Huber PE, Abdollahi A, Simon C. :Phenotype-assisted transcriptome analysis identifies FOXM1 downstream from Ras-MKK3-p38 to regulate in vitro cellular invasion. Oncogene. Dec 21. [Epub ahead of print], 2009

Lee TY, Muschal S, Pravda EA, Folkman J, Abdollahi A, Javaherian K.:Angiostatin regulates the expression of antiangiogenic and proapoptotic pathways via targeted inhibition of mitochondrial proteins. Blood. Aug 27;114(9):1987-98, 2009
comments in:
Mowery YM, Pizzo SV. The antitumorigenic trifecta. Blood. Aug 27;114(9):1727-8, 2009

Abiatari I, DeOliveira T, Kerkadze V, Schwager C, Esposito I, Giese NA, Huber P, Bergman F, Abdollahi A, Friess H, Kleeff J.:Consensus transcriptome signature of perineural invasion in pancreatic carcinoma. Mol Cancer Ther. Jun;8(6):1494-504, 2009

Schwager C, Wirkner U, Abdollahi A, Huber PE.:TableButler - a Windows based tool for processing large data tables generated with high-throughput methods. BMC Bioinformatics. Jul 29;10:235, 2009

Almog N, Ma L, Raychowdhury R, Schwager C, Erber R, Short S, Hlatky L, Vajkoczy P, Huber PE, Folkman J, Abdollahi A.:Transcriptional Switch of Dormant Tumors to Fast-Growing Angiogenic Phenotype. Cancer Research. 69:836-844, 2009

Domhan S, Muschal S, Schwager C, Morath C, Wirkner U, Ansorge W, Maercker C, Zeier M, Huber PE, Abdollahi A.:Molecular mechanisms of the antiangiogenic and antitumor effects of mycophenolic acid. Mol Cancer Ther. Jun;7(6):1656-68, 2008

Timke C, Zieher H, Roth A, Hauser K, Lipson KE, Weber KJ, Debus J, Abdollahi A, Huber PE.:Combination of vascular endothelial growth factor receptor/platelet-derived growth factor receptor inhibition markedly improves radiation tumor therapy. Clin Cancer Res. Apr 1;14(7):2210-9, 2008

Abdollahi A, Schwager C, Kleeff J, Esposito I, Domhan S, Peschke P, Hauser K, Hahnfeldt P, Hlatky L, Debus J, Peters JM, Friess H, Folkman J, Huber PE.:Transcriptional network governing the angiogenic switch in human pancreatic cancer. Proc Natl Acad Sci U S A Aug 16; Jul 31;104(31):12890-5. Epub 2007 Jul 24, 2007

Bedke J, Kiss E, Behnes CL, Popovic ZV, Heuser M, Stojanovic T, Sijmonsma T, Huber P, Domhan S, Muschal S, Abdollahi A, Gretz N, Grone HJ.:Anti-Inflammatory Effects of {alpha}v Integrin Antagonism in Acute Kidney Allograft Rejection. Am J Pathol. Aug 16; [Epub ahead of print], 2007

Abdollahi A, Hlatky L, Huber PE: Endostatin: The logic of antiangiogenic therapy. Drug Resist Updat 8: 59-74, 2005

Abdollahi A, Li M, Ping G, Plathow C, Domhan S, Kiessling F, Lee LB, McMahon G, Gröne HJ, Lipson KE, Huber PE: Inhibition of platelet-derived growth factor signaling attenuates pulmonary fibrosis. J Exp Med 201: 925-35 2005

Huber PE, Bischof M, Heiland S, Peschke P, Stoffregen C, Grone HJ, Debus J, Lipson K, Abdollahi A: Trimodal cancer treatment: beneficial effects of combined antiangiogenesis, radiation and chemotherapy. Cancer Res 65: 3643-55, 2005

Abdollahi A, Griggs DW, Zieher H, Roth A, Lipson KE, Saffrich R, Grone HJ, Hallahan DE, Reisfeld RA, Debus J, Niethammer AG, Huber PE: Inhibition of alpha(v)beta3 integrin survival signaling enhances antiangiogenic and antitumor effects of radiotherapy. Clin Cancer Res 11: 6270-9, 2005

Abdollahi A, Hahnfeldt P, Maercker C, Grone HJ, Debus J, Ansorge W, Folkman J, Hlatky L, Huber PE: Endostatin´s antiangiogenic signaling network. Mol Cell 13: 649-63, 2004

Abdollahi A, Lipson KE, Sckell A, Zieher H, Klenke F, Poerschke D, Roth A, Han X, Krix M, Bischof M, Hahnfeldt P, Grone HJ, Debus J, Hlatky L, Huber PE: Combined therapy with Direct and indirect angiogenesis inhibitors results in enhanced anti-angiogenic and anti-tumor effects. Cancer Res 63: 8890-98, 2003

Abdollahi A, Lipson KE, Han X, Krempien R, Trinh T, Weber KJ, Hahnfeldt P, Hlatky L, Debus J, Howlett AR, Huber PE. SU5416 and SU6668 decrease angiogenic effects of radiation-induced factor productions by tumor cells and amplify the direct anti-endothelial action of radiation in vitro. Cancer Res 63: 3755-63, 2003

 
 
 
 
 
 

 

 
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Impressum | Last update: 02/25/2010