Adrenal Gland Tumorigenesis

For over a decade the main focus of Dr. Christian G. Ziegler’s research group is on adrenal tumors and pre-clinical adrenal cancer models, with special focus on pheochromocytoma (PHEO). Within my two funded DFG projects (Zi 1362/2-1, 2-2; 2012-2018) we investigate novel therapeutic strategies for the treatment of PHEO in vitro and in vivo (1, 2). We specifically elucidated the role and significance of aberrantly expressed neuropeptide hormone receptors in adrenal diseases. Based on these initial in vitro studies we developed a novel mouse pheochromocytoma (MPC)-mcherry allograft model enabling in vivo-fluorescence imaging of tumor development. In this mouse model we could, as the first group so far, correlate tumor size with tumor-related renal monoamine secretion in preclinical PHEO models (3). Furthermore, our unique MPC-mCherry allograft model was successfully employed in a study focusing on preclinical diagnostic and targeted SSTR2 evaluations by long-lasting peptide somatostatin analogues (4). By multimodal imaging, including optical imaging, computed tomography (CT), magnet resonance imaging (MRI), and position emissions tomography (PET), we precisely followed tumour growth in vivo over a general observation period of 30 days. 

Adapted according to Ullrich and Ziegler et al., 2016 (4).

In our actual ongoing studies (currently funded by DFG: CRC/TRR 205 until end of 2021) we now evaluate combined and novel treatment strategies for PHEO based on our subcutaneous mcherry mouse model and on recently developed advanced bioluminescence i.v. PHEO models with different organ lesions, typical for the human disease. Furthermore, in our immune-compromised as well as -deficient mice we extended our theranostic strategies on pheochromocytoma tumor metabolism and novel immune-oncological approaches. All our studies are in close collaboration with the Helmholtzzentrum Dresden Rossendorf (HZDR), one of the very few European centers with the expertise and availability of a dedicated multimodal small animal imaging facility.

Additional important and very fruitful cooperations exist for many years with the noble laurate Andrew V. Schally (Miami Miller School of Medicine), Karel Pacak (NIH, Bethesda), Arthur Tischler (Tufts Medical Center, Boston) as well as with Graeme Eisenhofer (TUD).