PMID- 28736633
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231112
IS  - 2078-6891 (Print)
IS  - 2219-679X (Electronic)
IS  - 2078-6891 (Linking)
VI  - 8
IP  - 3
DP  - 2017 Jun
TI  - Biologics in gastrointestinal and pancreatic neuroendocrine tumors.
PG  - 457-465
LID - 10.21037/jgo.2016.12.09 [doi]
AB  - The development of biologic agents has ushered in a new era of precision 
      medicine, opening the door to new therapeutic options designed to intelligently 
      target cancer cells and their promoting factors, while leaving normal cells 
      relatively unharmed. Biologics for the treatment of neuroendocrine tumors (NETs) 
      have followed in the footsteps of regimens targeting pathways upregulated in 
      other cancers, including the vascular endothelial growth factor (VEGF) and the 
      mammalian target of rapamycin (mTOR). Through a number of clinical trials, the 
      mTOR inhibitor everolimus and the receptor tyrosine kinase (RTK) inhibitor 
      sunitinib were recently approved for NETs. Other biologics such as the VEGF-A 
      inhibitor bevacizumab have also demonstrated promising clinical activity in NETs. 
      Interestingly, though trials have demonstrated the efficacy of everolimus and 
      sunitinib in extending progression-free survival (PFS) in NETs, objective 
      response rates (RR) are uniformly low, indicating that the primary effect of 
      these drugs is maintenance of stable disease. Due to the relatively indolent 
      nature of the more common, well-differentiated variety of NETs, stable disease is 
      often a reasonable goal for NET patients. Well-differentiated NETs have been 
      shown to be poor responders to cytotoxic chemotherapy, underlining the important 
      role of biologics in treating and managing NETs and their hormonal symptoms. 
      Ongoing and future trials are investigating a wide variety of biologic compounds 
      in NETs, including other RTK inhibitors, mTOR pathway inhibitors, and immune 
      checkpoint inhibitors. Within this review, we will discuss major trials leading 
      up to the FDA approval of everolimus and sunitinib for NETs, as well as other 
      promising biologics currently under investigation in NET clinical trials.
FAU - Liu, Iris H
AU  - Liu IH
AD  - Stanford University School of Medicine, Stanford, CA, USA.
FAU - Kunz, Pamela L
AU  - Kunz PL
AD  - Stanford University School of Medicine, Stanford, CA, USA.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - China
TA  - J Gastrointest Oncol
JT  - Journal of gastrointestinal oncology
JID - 101557751
PMC - PMC5506272
OTO - NOTNLM
OT  - Neuroendocrine tumor (NET)
OT  - biologic
OT  - carcinoid
OT  - targeted therapy
COIS- Conflicts of Interest: Dr. PL Kunz is the PI on clinical trials with Dicerna, 
      Esanex, Oxigene, Advanced Accelerator Applications, Genentech, Ipsen, Lexicon 
      Pharmaceuticals, Merck and she serves on an Advisory Board for Ipsen and Lexicon. 
      Dr. IH Liu has no conflicts of interest to declare.
EDAT- 2017/07/25 06:00
MHDA- 2017/07/25 06:01
PMCR- 2017/06/01
CRDT- 2017/07/25 06:00
PHST- 2017/07/25 06:00 [entrez]
PHST- 2017/07/25 06:00 [pubmed]
PHST- 2017/07/25 06:01 [medline]
PHST- 2017/06/01 00:00 [pmc-release]
AID - jgo-08-03-457 [pii]
AID - 10.21037/jgo.2016.12.09 [doi]
PST - ppublish
SO  - J Gastrointest Oncol. 2017 Jun;8(3):457-465. doi: 10.21037/jgo.2016.12.09.