PMID- 32590358
OWN - NLM
STAT- MEDLINE
DCOM- 20210825
LR  - 20210825
IS  - 1479-6821 (Electronic)
IS  - 1351-0088 (Linking)
VI  - 27
IP  - 9
DP  - 2020 Sep
TI  - Preclinical drug studies in MEN1-related neuroendocrine neoplasms (MEN1-NENs).
PG  - R345-R355
LID - 10.1530/ERC-20-0127 [doi]
AB  - 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 beta-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.
FAU - Grozinsky-Glasberg, Simona
AU  - Grozinsky-Glasberg S
AD  - Neuroendocrine Tumor Unit, ENETS Center of Excellence, Department of 
      Endocrinology and Metabolism, Hadassah-Hebrew University Medical Center, 
      Jerusalem, Israel.
FAU - Lines, Kate E
AU  - Lines KE
AD  - Neuroendocrine Tumor Unit, ENETS Center of Excellence, Department of 
      Endocrinology and Metabolism, Hadassah-Hebrew University Medical Center, 
      Jerusalem, Israel.
FAU - Avniel-Polak, Shani
AU  - Avniel-Polak S
AD  - Neuroendocrine Tumor Unit, ENETS Center of Excellence, Department of 
      Endocrinology and Metabolism, Hadassah-Hebrew University Medical Center, 
      Jerusalem, Israel.
FAU - Bountra, Chas
AU  - Bountra C
AD  - Structural Genomics Consortium, University of Oxford, Oxford, UK.
FAU - Thakker, Rajesh V
AU  - Thakker RV
AD  - Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, 
      Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), Churchill 
      Hospital, Oxford, UK.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Endocr Relat Cancer
JT  - Endocrine-related cancer
JID - 9436481
SB  - IM
MH  - Female
MH  - Humans
MH  - Male
MH  - Multiple Endocrine Neoplasia Type 1/*drug therapy
MH  - Neuroendocrine Tumors/*drug therapy
OTO - NOTNLM
OT  - MEN1
OT  - endocrine neoplasia
OT  - neuroendocrine neoplasms
OT  - preclinical studies
EDAT- 2020/06/27 06:00
MHDA- 2021/08/26 06:00
CRDT- 2020/06/27 06:00
PHST- 2020/06/15 00:00 [received]
PHST- 2020/06/25 00:00 [accepted]
PHST- 2020/06/27 06:00 [pubmed]
PHST- 2021/08/26 06:00 [medline]
PHST- 2020/06/27 06:00 [entrez]
AID - ERC-20-0127.R2 [pii]
AID - 10.1530/ERC-20-0127 [doi]
PST - ppublish
SO  - Endocr Relat Cancer. 2020 Sep;27(9):R345-R355. doi: 10.1530/ERC-20-0127.