دورية أكاديمية
A New Medical Therapy for Multiple Endocrine Neoplasia Type 1?
| العنوان: | A New Medical Therapy for Multiple Endocrine Neoplasia Type 1? |
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| المؤلفون: | Boharoon H; Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK., Grossman A; Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London, UK. |
| المصدر: | TouchREVIEWS in endocrinology [touchREV Endocrinol] 2022 Nov; Vol. 18 (2), pp. 86-88. Date of Electronic Publication: 2022 Aug 23. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Touch Medical Media Ltd Country of Publication: England NLM ID: 101779126 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2752-5457 (Electronic) Linking ISSN: 27525457 NLM ISO Abbreviation: touchREV Endocrinol Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Reading, England : Touch Medical Media Ltd., [2021]- |
| مستخلص: | 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. Competing Interests: Disclosures: Hessa Boharoon and Ashley Grossman have no financial or non-financial relationships or activities to declare in relation to this article. (© Touch Medical Media 2022.) |
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| فهرسة مساهمة: | Keywords: Dihydroorotate dehydrogenase; leflunomide; multiple endocrine neoplasia type 1; neuroendocrine tumour; pancreas; therapy |
| تواريخ الأحداث: | Date Created: 20230125 Latest Revision: 20230202 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC9838189 |
| DOI: | 10.17925/EE.2022.18.2.86 |
| PMID: | 36694894 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2752-5457 |
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| DOI: | 10.17925/EE.2022.18.2.86 |