Molecular alterations and therapeutic targets in pancreatic neuroendocrine tumors

Human pancreatic neuroendocrine tumors (PanNETs) are a rare, deadly tumor type that is sporadic or arises in the background of a hereditary syndrome. A critical genetic event in sporadic tumors is inactivation of the gene menin 1 (MEN1) on chromosome 11, and indeed, PanNETs occur in patients with the hereditary syndrome multiple endocrine neoplasia type 1 (MEN1) due to germline mutations in the gene. Here, we review the recent progress in the field of molecular genetics and therapeutic targets of PanNETs. The key genomic alterations, including MEN1, ATRX/DAXX, mammalian target of rapamycin (mTOR), DNA damage and repair associated genes, vascular endothelial growth factor receptor (VEGFR) and SSTRs, and epigenetic aberrations in PanNETs are discussed. In addition, the commonly used preclinical models for PanNETs are enumerated.