title: Antiangiogenic Therapy in Pancreatic Neuroendocrine Tumors.
abstract: In recent years, many progresses have been pursued in the management of advanced pancreatic neuroendocrine tumor (pNET); most of them were prompted by increasing knowledge of biology of these neoplasms, including the identification of promising biological targets for therapy. PNETs belong to a group of rare neoplastic diseases. They originate from neuroendocrine system cells and are very heterogeneous regarding anatomic localization and aggressiveness. Recently, many efforts have been particularly focused on the identification of pathologic pathways and innovative drugs in order to treat patients with unresectable, metastatic disease, in progressive well-differentiated pNETs. Chemotherapy remains the mainstay of treatment of poorly-differentiated pNETs. The positive results obtained by sunitinib, a multi-targeted tyrosine kinase receptor inhibitor of vascular endothelial growth factor receptor (VEGFR) 1-3, platelet-derived growth factor receptor (PDGFR), c-kit, RET, colony stimulating factor-1 receptor (CSF-1R) and Fms-like tyrosine kinase 3 (FLT3), with direct antitumor and antiangiogenic effects, have highlighted the importance of tumor angiogenesis inhibition in controlling these tumors. Angiogenesis is a crucial process during tumor progression and plays a key role in development of metastasis. The role of angiogenesis in the malignant spread of pNET cells is finally supported by in vivo studies conducted on the RIP1-Tag2 mouse model. In this mini-review, we focus on the two pharmaceuticals that have given the most interesting results in clinical trials: bevacizumab and sunitinib. These drugs are changing the management of advanced pNETs.
authors: Department of Abdominal Oncology, Division of Medical Oncology, National Cancer Institute IRCCS "G. Pascale Foundation", Naples, Italy m.capozzi@istitutotumori.na.it.
authors: Monica
authors: M
authors: Capozzi
authors: Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, Italy.
authors: Claudia
authors: C
authors: VON Arx
authors: Department of Abdominal Oncology, Division of Medical Oncology, National Cancer Institute IRCCS "G. Pascale Foundation", Naples, Italy.
authors: Chiara
authors: C
authors: DE Divitiis
authors: Department of Abdominal Oncology, Division of Medical Oncology, National Cancer Institute IRCCS "G. Pascale Foundation", Naples, Italy.
authors: Alessandro
authors: A
authors: Ottaiano
authors: Department of Diagnostic Pathology and Laboratory, National Cancer Institute IRCCS "G. Pascale Foundation", Naples, Italy.
authors: Fabiana
authors: F
authors: Tatangelo
authors: Department of Abdominal Oncology, Division of Surgical Oncology, National Cancer Institute IRCCS "G. Pascale Foundation", Naples, Italy.
authors: Giovanni Maria
authors: GM
authors: Romano
authors: Department of Abdominal Oncology, Division of Medical Oncology, National Cancer Institute IRCCS "G. Pascale Foundation", Naples, Italy.
authors: Salvatore
authors: S
authors: Tafuto
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000068258:Bevacizumab / Q000627:therapeutic use; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D011758:Pyrroles / Q000627:therapeutic use; D000077210:Sunitinib
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D000068258:Bevacizumab; D000077210:Sunitinib
keywords: Neuroendocrine tumors; angiogenesis; bevacizumab; review; sunitinib