Abstract
Gastroenteropancreatic neuroendocrine tumors (GEP NETs) are a diverse group of tumors often characterized by somatostatin receptor type 2 (SSTR2) positivity. The objective of this article is to review basic information on GEP NETs and somatostatin receptors (SSTR) with a focus on SSTR2. The prognostic implications of the receptor, how epigenetic modifications play a role, and the diagnostic and therapeutic strategies available that rely on the somatostatin receptor including somatostatin analogs (SSAs), SSTR-based imaging, and peptide receptor radionuclide therapy (PRRT) are explored. While surgery is the only curative option, current therapy for SSTR2 positive GEP NETs is based on the use of SSAs which have been shown to both control symptoms and exert antiproliferative effects in SSTR2 positive GEP NETs. SSTR-based imaging offers numerous benefits over standard imaging techniques including revealing additional metastases, assessing response to therapy, and by demonstrating sufficient SSTR expression in tumors to render patients eligible for PRRT. PRRT has been shown to be an effective treatment in low grade, SSTR2 positive GEP NETs. Adjuncts are being investigated to synergize with PRRT and improve patient outcomes. Complete responses to SSA and PRRT are rare and SSTR2 negative tumors have limited treatment options. Given that GEP NETs have a low frequency of mutations and no mutations in SSTR2 have been identified, efforts are being made to investigate epigenetic regulations influencing SSTR2 expression as a future therapeutic option.