Neuroendocrine
neoplasms (NENs) occur usually as sporadic tumours; however, rarely, they may arise in the context of a hereditary syndrome, such as
multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder characterised by the combined development of pancreatic NENs (pNENs) together with parathyroid and anterior pituitary tumours. The therapeutic decision for sporadic pNENs patients is multi-disciplinary and complex: based on the grade and stage of the
tumor, various options (and their combinations) are considered, such as surgical excision (either curative or for debulking aims), biological drugs (
somatostatin analogues), targeted
therapies (
mTOR inhibitors or
tyrosine kinases (TK)/receptors inhibitors),
peptide receptor radioligand
therapy (PRRT),
chemotherapy, and liver-directed
therapies. However, treatment of MEN1-related NENs' patients is even more challenging, as these tumours are usually multifocal with co-existing foci of heterogeneous biology and malignant potential, rendering them more resistant to the conventional
therapies used in their sporadic counterparts, and therefore associated with a poorer prognosis. Moreover, clinical data using standard therapeutic options in MEN1-related NENs are scarce. Recent preclinical studies have identified potentially new targeted therapeutic options for treating MEN1-associated NENs, such as epigenetic modulators, Wnt pathway-targeting β-
catenin antagonists, Ras signalling modulators, Akt/mTOR signalling modulators, novel
somatostatin receptors analogues,
anti-angiogenic drugs, as well as MEN1 gene replacement
therapy. The present review aims to summarize these novel therapeutic opportunities for NENs developing in the context of MEN1 syndrome, with an emphasis on pancreatic NENs, as they are the most frequent ones studied in MEN1-NENs models to date; moreover, due to the recent shifting nomenclature of '
pituitary adenomas' to 'pituitary neuroendocrine
neoplasms', relevant data on MEN1-pituitary tumours, when appropriate, are briefly described.