Towards a new classification of gastroenteropancreatic neuroendocrine neoplasms

Neuroendocrine neoplasms (NENs) constitute a heterogeneous group of tumours that are each associated with varying clinical presentations, a different likelihood of progression, and a distinct prognosisThe 2010 WHO classification of NENs stratifies disease into NEN grade 1, NEN grade 2, neuroendocrine carcinoma (NEC) grade 3; this classification forms the basis of current treatment guidelinesMolecular profiling of tissue specimens is increasingly performed in clinical practice and provides information on genetic aberrations of potential therapeutic relevance; although with limited clinical value to dateThe 'driver' mutations in gastroenteropancreatic NENs, which might be important targets for new therapies, remain to be identified; however, the PI3K/AKT/mTOR axis has been identified as a key oncogenic signalling pathwayNENs can be treated using mTOR inhibitors (rapalogs including everolimus and temsirolimus), but resistance eventually develops via escape mechanisms that warrant further investigation in order to develop novel therapeutic strategiesThe 2010 WHO classification will continue to guide the management of NENs; however, information from molecular profiling of tumours, 'liquid biopsies' (including circulating mRNA measurements), and molecular imaging might improve patient outcomes