Current status and perspectives of targeted therapy in well-differentiated neuroendocrine tumors.
Although neuroendocrine tumors (NET) are a relatively rare malignancy, the reported incidence is increasing, and some of the current treatment options are limited in their efficacy. Standard first-line therapy for metastatic small bowel NET includes somatostatin analogs. Although these agents can provide symptom relief and can delay disease progression in many patients, ultimately, new treatments are required for patients with progressive disease. In recent years, there has been considerable interest in developing agents specifically targeted against some of the pathways known to be involved in cancer cell growth, survival and invasion. In 2011, the mammalian target of rapamycin (mTOR) inhibitor everolimus and the tyrosine kinase inhibitor sunitinib were approved for the treatment of pancreatic NET. Clinical trials evaluating novel targeted agents are ongoing, both as single agents and in combination regimens. We review the current clinical status of these potential new treatments and highlight those with particular promise for the management of well-differentiated NET.
Division of Hematology, Oncology, and Blood and Marrow Transplantation, Neuroendocrine Tumor Program, University of Iowa Hospitals and Clinic, Iowa City, Iowa 52242, USA.
Boris G
BG
Naraev
Jonathan R
JR
Strosberg
Thorvardur R
TR
Halfdanarson
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000627:therapeutic use; D002454:Cell Differentiation; D066246:ErbB Receptors / Q000378:metabolism; D000068338:Everolimus; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007191:Indazoles; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D058990:Molecular Targeted Therapy / Q000379:methods*; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology*; D009536:Niacinamide / Q000031:analogs & derivatives; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010671:Phenylurea Compounds; D011725:Pyridines / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000378:metabolism; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007155:Immunologic Factors; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D017481:Receptors, Somatostatin; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; C516667:pazopanib; D000068338:Everolimus; D000077157:Sorafenib; C546842:MTOR protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D058570:TOR Serine-Threonine Kinases; D006655:Histone Deacetylases; D000077210:Sunitinib; D020123:Sirolimus