The strong translational background of our research dates back about two decades and was supported by the German Cancer Aid providing a professor position in the Surgical Clinic, which was then institutionalized by the Medical Faculty. In 2009 the Division of Molecular Oncology became the founding body of the newly established Institute for Experimental Cancer Research.
Our research is based on a very comprehensive biobank from gastrointestinal, hepatobiliary and lung cancer as well as clinically adapted murine tumor models, which are monitored by multi-modal molecular imaging techniques. Besides biomarker (CTCs, DTCs, exosomes) studies in CRC (supported by the Excellence Cluster “Inflammation at Interfaces”) we are mainly interested in PDAC. Here we focus – based on extensive studies on apoptosis resistance mechanisms – on non-apoptotic, pro-inflammatory mechanisms of death receptor signaling. Recently we uncovered a surprising novel mechanism of TRAIL-Receptors, which gaine an oncogenic function upon nuclear localization. Here, TRAIL-R2 influences the maturation of LET7 microRNAs and thus drives proliferation and invasion of cancer cells.
Non-canonical function of TRAIL-Receptors also impacts the transportom and this is in focus of our IonTraC project.
Egberts, J. H., V. Cloosters, A. Noack, B. Schniewind, L. Thon, S. Klose, B. Kettler, C. Forstner, C. Kneitz, J. Tepel, D. Adam, H. Wajant, H. Kalthoff, A. Trauzold. 2008. Anti-Tumor Necrosis Factor Therapy Inhibits Pancreatic Tumor Growth and Metastasis. Cancer Res. 68: (5), 1443-50.
Lemke J, Noack A, Adam D, Tchikov V, Bertsch U, Röder C, Schütze S, Wajant H, Kalthoff H, Trauzold A. TRAIL signaling is mediated by DR4 in pancreatic tumor cells despite the expression of functional DR5. Journal of Molecular Medicine 2010 88(7):729-40.
Haselmann V, Kurz A, Bertsch U, Hübner S, Olempska-Müller M, Fritsch J, Häsler R, Pickl A, Fritsche H, Annewanter F, Engler C, Fleig B, Bernt A, Röder C, Schmidt H, Gelhaus C, Hauser C, Egberts JH, Heneweer C, Rohde AM, Böger C, Knippschild U, Röcken C, Adam D, Walczak H, Schütze S, Janssen O, Wulczyn FG, Wajant H, Kalthoff H, Trauzold A. Nuclear Death Receptor TRAILR2 Inhibits Maturation of Let-7 and Promotes Proliferation of Pancreatic and Other Tumor cells.
Voigt S, Philipp S, Davarnia P, Winoto-Morbach S, Röder C, Arenz C, Trauzold A, Kabelitz D, Schütze S, Kalthoff H, Adam D. TRAIL-induced programmed necrosis as a novel approach to eliminate tumor cells. BMC Cancer 2014 Feb 7;14(1):74
Goumas F, Holmer R, Egberts J, Gontarewicz A, Heneweer C, Geisen U, Hauser C, Mende MM, Legler K, Röcken C, Becker T, Waetzig G, Rose-John S, Kalthoff H. Inhibition of IL-6 signaling significantly reduces primary tumor growth and recurrencies in orthotopic xenograft models of pancreatic cancer. Int J Cancer 2015, epub ahead of print.
Results and Problems in Cell Differentiation Volume 49, 2009
Death Receptors and Cognate Ligands in Cancer
Holger Kalthoff (ed.), Springer