Role of Somatostatin Receptor in Pancreatic Neuroendocrine Tumor Development, Diagnosis, and Therapy

Abstract

Pancreatic neuroendocrine tumors (pNETs) are rare and part of the diverse family of neuroendocrine neoplasms (NENs). Somatostatin receptors (SSTRs), which are widely expressed in NENs, are G-protein coupled receptors that can be activated by somatostatins or its synthetic analogs. Therefore, SSTRs have been widely researched as a diagnostic marker and therapeutic target in pNETs. A large number of studies have demonstrated the clinical significance of SSTRs in pNETs. In this review, relevant literature has been appraised to summarize the most recent empirical evidence addressing the clinical significance of SSTRs in pNETs. Overall, these studies have shown that SSTRs have great value in the diagnosis, treatment, and prognostic prediction of pNETs; however, further research is still necessary.

Keywords: pancreatic neuroendocrine tumor; peptide receptor radionuclide therapy; somatostatin analog; somatostatin receptor; somatostatin receptor imaging.

Figure 1

A schematic presentation of theranostics with radiolabeled SSAs that target the SSTRs. The radiopharmaceutical element is comprised of the targeting fraction (SSA) and a chelator that forms a steady composite with the radionuclide. Radiotheranostics consists of diagnostic (panel on the left) and therapeutic (panel on the right) aspects.

Figure 2

Schematic representation of SSTR-targeted therapy. (A–C) represent the intracellular signaling pathways modulated by SSA/SST. (D) represents the schematic of peptide receptor radionuclide therapy (PRRT). Blue arrows, activation; red arrows, inhibition; ↑, increase; ↓, decrease; ACL, adenylate cyclase; AKT, protein kinase B; BAX, B-cell lymphoma 2 (BCL2)-associated X protein; Ca2+, calcium; G, G protein; JNK, c-Jun N-terminal kinases; K+, potassium; MEK, mitogen-activated protein kinase kinase; NFκB, nuclear factor kappa B; PI3K, phosphoinositide 3 kinase; PTPη, phosphotyrosine phosphatase η; raf, rapidly accelerated fibrosarcoma kinase; ras, RAS kinase; SHP1, Src homology phosphatase 1; SHP2, Src homology phosphatase 2; Src, Rous sarcoma oncogene; SSAs, somatostatin analogues; SST, somatostatin; SSTR, somatostatin receptor; Vdc, voltage-dependent channel; VEGF, vascular endothelial growth factor; Zac1, zinc finger protein regulator of apoptosis and cell cycle arrest.