Title:Molecular Targeted Therapy in Enteropancreatic Neuroendocrine Tumors: From Biology to Clinical Practice
Volume: 21
Issue: 8
Author(s): N. Fazio, A. Scarpa and M. Falconi
Affiliation:
Keywords:
Molecular targeted therapies, NETs, neuroendocrine tumors, GEP, everolimus, sunitinib, bevacizumab, mTOR.
Abstract: Advanced enteropancreatic (EP) neuroendocrine tumors (NETs) can be treated with several different therapies,
including chemotherapy, biotherapy, and locoregional treatments. Over the last few decades, impressive progress has been
made in the biotherapy field. Three main druggable molecular targets have been studied and developed in terms of therapy:
somatostatin receptor (sstr), mammalian target of rapamycin (mTOR), and angiogenic factors. In particular, research
has moved from the old somatostatin analogs (SSAs), such as octreotide (OCT) and lanreotide (LAN), specifically binding
to the sstr-2, to the newer pasireotide (PAS), which presents a wider sstr spectrum. Over the last ten years, several molecular
targeted agents (MTAs) have been studied in phase II trials, and very few of them have reached phase III. The
mTOR inhibitor everolimus and the multitargeted inhibitor sunitinib have been approved for clinical use by the FDA and
EMA in advanced well/moderately-differentiated (WD, MD) progressive pancreatic neuroendocrine tumors (PNETs), on
the basis of the positive results of two international large randomized phase III trials vs. placebo. Bevacizumab has been
studied in a large US phase III trial vs. interferon (IFN)-alfa2b, and results are pending. In this review, the biological and
clinical aspects of MTAs introduced into clinical practice or which are currently in an advanced phase of clinical investigation
are addressed.
