PMID- 36694894
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230202
IS  - 2752-5457 (Electronic)
IS  - 2752-5457 (Linking)
VI  - 18
IP  - 2
DP  - 2022 Nov
TI  - A New Medical Therapy for Multiple Endocrine Neoplasia Type 1?
PG  - 86-88
LID - 10.17925/EE.2022.18.2.86 [doi]
AB  - Pancreatic neuroendocrine tumours (pNETs) are a major manifestation of multiple 
      endocrine neoplasia type 1 (MEN1), and the most significant cause of morbidity 
      and mortality in this disorder. There is some evidence that the early use of 
      somatostatin analogues can retard progression, especially of small 
      non-functioning tumours, but there are no other prophylactic therapies for 
      patients, and the treatment of metastatic disease is similar to that for sporadic 
      pNETs. A recent study has shown that in cell line and animal models, MEN1 
      mutations lead to an upregulation of the enzyme dihydroorotate dehydrogenase 
      (DHODH), which is involved in increasing precursor metabolites for the synthesis 
      of pyrimidines. In these studies, blockade of this pathway by various means, 
      including the DHODH inhibitor leflunomide, attenuates cell growth and tumour 
      progression, suggesting a critical dependence on DHODH specifically in 
      MEN1-mutated tissue. Preliminary clinical studies in three patients with MEN1 and 
      pNETs have indicated some therapeutic potential of this drug, which has 
      previously been used for some years in patients with rheumatoid arthritis. It is 
      suggested that further clinical trials of this re-purposed drug are indicated to 
      evaluate its potential for the treatment of patients with MEN1 and pNETS. This 
      article describes the clinical problem of MEN1 and pNETs, and reviews the recent 
      publication reporting on these initial results.
CI  - (c) Touch Medical Media 2022.
FAU - Boharoon, Hessa
AU  - Boharoon H
AD  - Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, 
      London, UK.
FAU - Grossman, Ashley
AU  - Grossman A
AD  - Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, 
      London, UK.
LA  - eng
PT  - Journal Article
DEP - 20220823
PL  - England
TA  - touchREV Endocrinol
JT  - TouchREVIEWS in endocrinology
JID - 101779126
PMC - PMC9838189
OTO - NOTNLM
OT  - Dihydroorotate dehydrogenase
OT  - leflunomide
OT  - multiple endocrine neoplasia type 1
OT  - neuroendocrine tumour
OT  - pancreas
OT  - therapy
COIS- Disclosures: Hessa Boharoon and Ashley Grossman have no financial or 
      non-financial relationships or activities to declare in relation to this article.
EDAT- 2023/01/26 06:00
MHDA- 2023/01/26 06:01
PMCR- 2022/11/01
CRDT- 2023/01/25 01:50
PHST- 2022/06/07 00:00 [received]
PHST- 2022/07/29 00:00 [accepted]
PHST- 2023/01/25 01:50 [entrez]
PHST- 2023/01/26 06:00 [pubmed]
PHST- 2023/01/26 06:01 [medline]
PHST- 2022/11/01 00:00 [pmc-release]
AID - 10.17925/EE.2022.18.2.86 [doi]
PST - ppublish
SO  - touchREV Endocrinol. 2022 Nov;18(2):86-88. doi: 10.17925/EE.2022.18.2.86. Epub 
      2022 Aug 23.