Advances in small bowel neuroendocrine neoplasia

PURPOSE OF REVIEW: This review aims at summarizing progress in clinical trials and basic science redefining the diagnosis and treatment of well differentiated small intestine neuroendocrine tumors (SI-NET). RECENT FINDINGS: Two clinical trials demonstrated antitumor activity of the long-acting somatostatin analogues octreotide long-acting release and lanreotide for advanced SI-NET. The mammalian target of rapamycin (mTOR) inhibitor everolimus is another treatment option for patients with SI-NET, but awaits definitive proof of benefit in the ongoing RAD001 In Advanced Neuroendocrine Tumors study (RADIANT-4). Two whole exome/genome-sequencing studies reported in the past year provided the first genome-wide analysis of large sets of SI-NET at nucleotide resolution. Candidate therapeutically relevant alterations were found to affect SRC, SMAD genes, aurora kinase A, epidermal growth factor receptor, heat shock protein 90, and platelet-derived growth factor receptor as well as mutually exclusive amplification of RAC-alpha serine/threonine-protein kinase (AKT1) or AKT2 and other alterations of PI3K/Akt/mTOR signaling genes. The gene CDKN1B is inactivated by small insertions/deletions in 8% of patients with SI-NET suggesting cell cycle inhibitors as new candidate drugs for SI-NET. Circulating tumor cells and tumor-derived RNA in the blood are promising clinical tests for SI-NET. SUMMARY: Clinical and genomic research may merge in the near future to re-shape clinical trials and to define the 'personalized' treatment options for patients with SI-NET.