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Department of Medicine III

The research at the department of medicine III (Med. Klinik und Poliklinik III- MKIII) focusses on three areas: (i) understanding the biology and improving the diagnosis and treatment of tumors causing endocrine hypertension; (ii) investigating the interface between mutations affecting energy pathway components and disruptions to metabolism as contributors to tumorigenesis and targets for therapy; and (iii) elucidating the molecular mechanisms and involved signaling pathways in bone metastases, a frequent complication in patients with advanced breast or prostate cancer.

In detail, (i) efforts directed towards endocrine hypertension focus on primary aldosteronism, Cushing’s syndrome, and pheochromocytomas. Here, research involves steroid profiling for diagnosis of the tumors and subtype classification to guide therapy. In addition, our research covers improvements to diagnostics, genetics, pathways of tumorigenesis, and use of model systems for new therapeutic interventions. Investigations exploring the interface between genetics and altered energy pathway metabolism (ii) are specifically based on work involving tumors due to mutations of Krebs cycle components. The national research consortium 1586 (SKELMET) aims to investigate the molecular mechanisms of skeletal homing of breast and prostate cancer cells and the anti-tumor potential of specific metabolic and signaling pathways (iii). The mechanisms why these cancers metastasize to bone are still incompletely understood and therapeutic intervention is limited. We investigate mesenchymal and osteogenic pathways in bone metastases using cancer cell lines, animal models, and molecular imaging. Furthermore, we aim to identify and validate novel targets that have the potential to translate into an improved patient care, by targeting the mevalonate pathway and the Wnt signaling.

Pamporaki C, Hamplova B, Peitzsch M, Prejbisz A, Beuschlein F, Timmers H, Fassnacht M, Klink B, Lodish M, Stratakis C, Huebner A, Fliedner S, Robledo M, Sinnott R, Januszewicz A, Pacak K, Eisenhofer G. Characteristics of Pediatric vs Adult Pheochromocytomas and Paragangliomas. J Clin Endocrinol Metab, April 2017, 102(4):1122–1132

Göbel A, Thiele S, Browne AJ, Rauner M, Zinna VM, Hofbauer LC, Rachner TD. Combined inhibition of the mevalonate pathway with statins and zoledronic acid potentiates their anti-tumor effects in human breast cancer cells. Cancer Lett. 2016;375:162-71. 

Eisenhofer G, Dekkers T, Peitzsch M, Dietz AS, Bidlingmaier M, Treitl M, Williams TA, Bornstein SR, Haase M, Rump LC, Willenberg HS, Beuschlein F, Deinum J, Lenders JW, Reincke M. Mass spectrometry-based adrenal and peripheral venous steroid profiling for subtyping primary aldosteronism. Clin Chem. 2016;62:514-24.

Thiele S, Göbel A, Rachner TD, Fuessel S, Froehner M, Muders MH, Baretton GB, Bernhardt R, Jakob F, Glüer CC, Bornhäuser M, Rauner M, Hofbauer LC. WNT5A has anti-prostate cancer effects in vitro and reduces tumor growth in the skeleton in vivo. J Bone Miner Res. 2015;30:471-80.

Hofbauer LC, Rachner TD, Coleman RE, Jakob F. Endocrine aspects of bone metastases. Lancet Diabetes Endocrinol. 2014; 2:500-12.

Lenders JW, Duh QY, Eisenhofer G, Gimenez-Roqueplo AP, Grebe SK, Murad MH, Naruse M, Pacak K, Young WF Jr; Endocrine Society. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99:1915-42.