Pancreatic Neuroendocrine Tumors: A Focus on the Current Classification and Molecular Targeted Therapy

AB S TRA C T Although their incidence has been rising over the last decades, pancreatic neuroendocrine tumors (PNETs) are relatively uncommon, accounting for less than 5% of all primary pancreatic malignancies. They are classified based on morphological and biological characteristics. The World Health Organization (WHO) classification from 2000 subcategorizes gastroenteropancreatic neuroendocrine tumors into welldifferentiated tumors, well-differentiated carcinomas, and poorly differentiated carcinomas; the TNM staging system from 2006 considers three ‘‘G’’ groups based on the Ki-67 level and three ‘‘T’’ groups related to the size. Retrospective analyses confirmed the prognostic relevance of both WHO and TNM staging systems for PNETs. As for treatment, chemotherapy, somatostatin analogs, interferon, and peptide radioreceptor therapy can have a role in PNETs. Over the last decade several molecular targeted agents have been studied. Among them sunitinib and everolimus are in the most advanced phase of clinical investigation. This is a literature review, based on a Medline search for pancreatic neuroendocrine tumor and carcinoma, which will focus on the clinical importance of classifications and the advances of molecular targeted therapies in PNETs.