TY - JOUR
T1 - Molecular targeted therapy in enteropancreatic neuroendocrine tumors
T2 - From biology to clinical practice
AU - Fazio, N.
AU - Scarpa, A.
AU - Falconi, M.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Bevacizumab
KW - Everolimus
KW - GEP
KW - Molecular targeted therapies
KW - MTOR
KW - NETs
KW - Neuroendocrine tumors
KW - Sunitinib
UR - http://www.scopus.com/inward/record.url?scp=84896374336&partnerID=8YFLogxK
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U2 - 10.2174/09298673113209990237
DO - 10.2174/09298673113209990237
M3 - Article
C2 - 23992320
AN - SCOPUS:84896374336
VL - 21
SP - 1017
EP - 1025
JO - Current Medicinal Chemistry
JF - Current Medicinal Chemistry
SN - 0929-8673
IS - 8
ER -