Benutzerspezifische Werkzeuge

Project 10

Novel Strategies of Targeted Multimodal/Combined Therapy of Pheochromocytoma

Pheochromocytoma (PHEO) is a rare but potentially lethal neuroendocrine tumour arising from chromaffin cells in the adrenal medulla and tumours of extra-adrenal sympathetic and parasympathetic paraganglia producing catecholamines. PHEO frequently overexpresses peptide hormone receptors, like SSTR2, LHRH-R; α-, β-, and dopamine receptors, cell membrane norepinephrine and LAT1-transporter systems that all are potential targets for highly specific radionuclide-based and cytotoxic therapeutics. PHEO represents tumours with oxidative phosphorylation defects due to the mutation of succinate dehydrogenase, which results in the shift from oxidative phosphorylation to aerobic glycolysis. This is a supporting factor to overexpress mediators of chemo- or radioresistence, e.g., the cyclooxygenase-2 in PHEO. The multidrug and toxic compound extrusion (MATE) family transporters in PHEO prevent long-time therapy by cytostatic compounds. All these PHEO characteristics increase the therapy resistance of this tumour entity. Therefore, is the combination of targeted radiotherapy with modulation of the radioresistance by, e.g., selective COX-2 inhibitors and cytotoxic therapy including the specific targeting of aberrantly expressed neuropeptide hormone receptors, mandatory.

The project essentially will include peptide and metabolic tumour imaging to functionally evaluate the tumour control.