Medical Scientist-Programm 2024

Thema: "Molecular characterization of the effects and side effects of the pan-somatostatin analog pasireotide"

Zusammenfassung:
Early detection of malignant tumors and their targeted treatment remains a major challenge for oncologists. Receptors for regulatory peptide hormones can be expressed at considerable densities on certain human tumors. To date, the five G protein-coupled receptors for somatostatin (SST1-SST5) have been prototypes for the development of such targeted therapies. In fact, overexpression of SST receptors is the molecular basis for the use of stable somatostatin analogs such as octreotide (SST2) and pasireotide (SST1, SST2, SST3, SST5) in the diagnosis and treatment of neuroendocrine tumors. Although pasireotide displays superior therapeutic effects compared to octreotide, its clinical use is limited by serious side effects such as induction of hyperglycemia by an unknown molecular mechanism. Therefore, a systematic analysis of the pharmacological target structure(s) of pan-somatostatin analogs is urgently needed. We have developed a humanized SST5 knockin mouse and an SST5 knockout mouse line. These mouse models will enable us to analyze which effects of pasireotide and other pan-somatostatin analogs are mediated via the SST5 receptor. In particular, these studies should show whether the known action profile of pasireotide is typical for all pan-somatostatin analogs or whether it is possible to develop pan-somatostatin analogs with fewer side effects.