Antiproliferative Systemic Therapies for Metastatic Small Bowel Neuroendocrine Tumours

Somatostatin and Its Receptor System in Colorectal Cancer

“…Clinical application of somatostatin has been limited by its very short half-life (<3 min), necessitating continuous intravenous infusion. Hence, a number of SAAs with a longer half-life (1.5–2 h) are applied in radiolabeled somatostatin analogue/peptide receptor radionuclide therapy (PRRT) [ 23 , 25 , 26 , 58 , 217 , 236 , 237 , 238 ]. Moreover, while the native SST binds to all SSTRs, OCT binds with high affinity to SST2 and SST5 [ 239 ].…”

“…Furthermore, the SRIF system is characterized by a strong antiproliferative activity, increasing cell apoptosis and inhibiting angiogenesis in most of the cancerous tissues [ 12 , 16 , 17 , 18 , 19 , 20 ]. This property is already used in clinical practice [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. SST acts through the activation of five membrane receptors (SSTRs/SSTs), belonging to the G protein-coupled receptor (GPCR) family [ 12 , 16 , 19 , 24 , 27 , 28 ].…”

Predictive Factors for Resistant Disease with Medical/Radiologic/Liver-Directed Anti-Tumor Treatments in Patients with Advanced Pancreatic Neuroendocrine Neoplasms: Recent Advances and Controversies

“…The prognosis in patients with advanced pancreatic neuroendocrine neoplasms (panNENs) has been generally poor and, until recently, there has been little improvement, mainly due to the lack of new therapeutic approaches which have led to effective anti-tumor treatment activity in these patients [ 7 , 9 , 11 , 12 , 13 , 14 , 15 ]. In the past decade, however, there has been significant advances, not only in the treatment approaches for panNEN patients with advanced disease, the recognition into the pathogenesis of the acquired and primary resistance to anti-tumor treatment which is an increasing problem, but also in the diagnosis, management and overall treatment of panNENs, as well as other NENs, which is beginning to influence survival rates in these patients [ 7 , 11 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. We have recently analyzed both these advances and controversies in identifying prognostic factors for the overall management of panNEN patients, as well as for surgical outcomes [ 7 ].…”

“…Recently, two additional Phase 3 studies have shown the anti-tumor effectiveness of another multityrosine kinase receptor inhibitor, surufatinib [ 33 ] in both advanced panNENs [ 34 ] and extrapancreatic NENs (carcinoids) [ 35 ]. PanNENs ectopically overexpress somatostatin receptors type 1–5 (SSTR 1–5) and numerous studies showed their activation has anti-tumor and anti-secretory effects in NENs [ 22 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. Like recent studies demonstrating that the somatostatin analogue (SSA) octreotide had an anti-tumor effect extending PFS in ileal carcinoids and other tumors [ 22 , 37 , 38 , 40 , 45 ], the long acting SSA lanreotide demonstrated similar anti-tumor activity in a recent Phase 3 trial involving patients with advanced gastroenteropancreatic NENs (GEP-NENs), in addition to its having an anti-secretory effect [ 22 , 37 , 46 ].…”

“…PanNENs ectopically overexpress somatostatin receptors type 1–5 (SSTR 1–5) and numerous studies showed their activation has anti-tumor and anti-secretory effects in NENs [ 22 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ]. Like recent studies demonstrating that the somatostatin analogue (SSA) octreotide had an anti-tumor effect extending PFS in ileal carcinoids and other tumors [ 22 , 37 , 38 , 40 , 45 ], the long acting SSA lanreotide demonstrated similar anti-tumor activity in a recent Phase 3 trial involving patients with advanced gastroenteropancreatic NENs (GEP-NENs), in addition to its having an anti-secretory effect [ 22 , 37 , 46 ]. PanNENs as well as NENs in other locations and many more common neoplasms frequently ectopically overexpress various G-protein coupled receptors, and these are increasingly being used to not only localized these tumors using various receptor ligands, as well as for targeted delivery of cytotoxic compounds [ 47 , 48 , 49 , 50 , 51 , 52 , 53 ].…”