SFB 773:  Understanding and Overcoming Therapy Resistance of Solid Tumours

• Subject Area: Medicine ; Biology
• Term: from 2008 to 2013
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 35654125

The Collaborative Research Centre is devoted to the understanding of molecular mechanisms of treatment resistance of solid human tumours and to the exploration of innovative treatment approaches to overcome treatment resistance by an interdisciplinary approach. While important therapeutic improvements including even curative approaches have been developed for some lymphomas and leukemias, this does not apply for most solid tumours. A major reason for this is the development of resistance to conventional therapies.
Therefore, the major focus of the Collaborative Research Centre is the analysis of intrinsic resistance mechanisms at the molecular level. All project leaders share a profound interest in understanding the molecular and cellular mechanisms, which mediate solid tumour cell resistance to adjuvant non-surgical modalities of tumour therapy, primarily radiotherapy and chemotherapy.
One major cause of therapy resistance is the deficient activation of cell death processes in tumour cells. Therefore, a number of projects investigate the impact of apoptotic but also of non-apoptotic forms of cell death such as autophagic cell death. In addition, the mechanisms are studied that by activation of senescence programmes inhibit tumour cell division. Another focus is the investigation of survival signalling pathways that also contribute to uncontrolled tumour growth.
Finally, the network programme is dedicated to investigate the role of tumour stem cells that represent an attractive target for overcoming therapy resistance.
Using different approaches the Collaborative Research Centre will investigate the molecular processes of epigenetic gene regulation, protein modifications, DNA-repair, cell cycle control as well as their interplay with cell death and proliferation of tumour cells. These molecular and cellular events are studied at a single cell level and in animal models using molecular imaging. Following their evaluation in preclinical models, these innovative treatment strategies shall be transferred into clinical phase I/II trials in cooperation with the Comprehensive Cancer Center (CCC) Tübingen.

• DFG Programme: Collaborative Research Centres

Completed projects

• A01 - Role of SGK isoforms in apoptosis, tumor growth and resistance of solid tumors to therapy (Project Head Lang, Florian )
• A02 - Ca2+-activated K+ channels as novel targets for anti-neoplastic therapy: role in tumor proliferation and resistance to cytotoxic drugs (Project Head Ruth, Peter )
• A03 - Identification of anticancer drugs that target autophagy in therapy-resistant tumor cells (Project Heads Nordheim, Alfred ;  Proikas-Cezanne, Tassula )
• A04 - Interaction of nuclear receptors with the beta-catenin-dependent signaling cascade: consequences for tumor cell survival (Project Head Schwarz, Michael )
• A06 - Modulation of the sphingolipid pathway to resolve resistance to therapy in experimental gliomas (Project Heads Tabatabai, Ghazaleh ;  Tatagiba, Marcos )
• A07 - Reprogramming melanoma cells and melanoma stem cell-like cells by embryonic morphogens: impact on drug resistance (Project Heads Busch, Christian ;  Garbe, Claus )
• B02 - Interaction of EGFR and DNA repair processes: Relevance for the radioresistance of solid tumors (Project Head Rodemann, H. Peter )
• B03 - Epigenetic reprogramming: innovative concept to overcome resistance to therapy in gastrointestinal oncology (Project Head Bitzer, Michael )
• B04 - The role of ubiquitin-ligases and YB-1 for resistance to therapy of papillomavirus-infected tumor cells (Project Head Iftner, Thomas )
• B05 - Regulation of irradiation and chemoresistance by microRNA expression (Project Heads Schmitz, Ingo ;  Schulze-Osthoff, Klaus )
• B06 - Molecular switches between premature senescence and apoptosis in anticancer treatment (Project Heads Essmann, Frank ;  Schulze-Osthoff, Klaus )
• C01 - Identification of novel apoptosis signaling pathways for the elimination of anticancer drug resistant tumors (Project Heads Stork, Björn ;  Wesselborg, Sebastian )
• C02 - The viral E8^E2C protein as a novel therapy for virus-induced carcinomas (Project Head Stubenrauch, Frank )
• C03 - Oncolysis-based multimodal concepts for breaking resistance to therapy in GI oncology (Project Head Lauer, Ulrich M. )
• C04 - Selective induction of apoptosis in tumor cells by bispecific antibodies directed to tenascin and the death receptor CD95/Fas/APO-1 (Project Head Jung, Gundram )
• C05 - The impact of targeting PI3K/Akt signaling on chemoresistance in melanoma (Project Heads Meier, Friedegund ;  Schittek, Birgit )
• C06 - Identification and targeting of self-renewal pathways in cancer stem cells to overcome drug resistance (Project Heads Kopp, Hans-Georg ;  Lengerke, Claudia )
• Z01 - Core-Project Molecular Imaging (Project Heads Claussen, Claus D. ;  Machulla, Hans-Jürgen ;  Pichler, Bernd )
• Z02 - Service Facility Micromorphology (Project Head Schaller, Martin )
• Z03 - Administrative Office (Project Head Wesselborg, Sebastian )
• Z04 - Integrated Graduate School "Molecular oncology" (Project Heads Iftner, Thomas ;  Wesselborg, Sebastian )

• Applicant Institution: Eberhard Karls Universität Tübingen
• Spokespersons: Professor Dr. Klaus Schulze-Osthoff; Professor Dr. Sebastian Wesselborg, until 8/2012