Novel therapeutic strategies for the treatment of pheochromocytoma

Pheochromocytoma is a rare but potentially lethal chromaffin cell tumor. The prognosis for malignant pheochromocytoma is particularly poor and there are currently no effective treatments. Interestingly, peptide hormone receptors are frequently overexpressed on endocrine tumor cells and can be specifically targeted by highly effective anti-tumor peptide analogs. Our actual study focuses on two endocrinologically relevant mouse pheochromocytoma cell lines, one more malignant and one more benign one as well as on mouse models of pheochromocytoma, which our group currently establishes.
First, we could demonstrate significant anti-tumor effects mediated by cytotoxic somatostatin analogs AN-162 and AN-238, by LHRH antagonist Cetrorelix and cytotoxic LHRH analog AN-152 as well as by GHRH antagonist MIA-602 targeting their respective receptors on mouse pheochromocytoma cells (MPC). Furthermore, similar anti-tumor effects were evidenced also for AN-152 and MIA-602 on more aggressive tumor tissue-derived (MTT) cells.
Second, we established a subcutaneous mouse model of pheochromocytoma for optimization of parametric tumor imaging in vivo. Tumor volume, morphology, metabolic activity and peptide receptors are evaluated using PET/MR and PET/CT imaging as well as fluorescence and bioluminescence imaging after injection of mCherry or luciferase transduced MPC cell lines. Furthermore, we are establishing an intravenous mouse model of pheochromocytoma to test the most effective peptide analogs in vivo. Ex vivo characterization of mouse pheochromocytomas demonstrated that peptide hormone receptors are still expressed during tumor growth in mice.
Altogether, our current investigation provides further evidence for the usefulness of targeted peptide hormone receptor therapy as a potential new option for future treatment of malignant pheochromocytoma