Chemoprevention with Somatuline© Delays the Progression of Pancreatic Neuroendocrine Neoplasms in a Mouse Model of Multiple Endocrine Neoplasia Type 1 (MEN1)

Lopez, Caroline; Joos, Barbara; Bartsch, Detlef K.; Manoharan, Jerena; Albers, Max B.; Slater, Emily P.; Bollmann, Carmen; Roth, Sylvia; Bayer, A.; Fendrich, Volker

doi:10.1007/s00268-018-4839-8

Cited by 11 publications

(2 citation statements)

References 43 publications

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“…Other interventions to prevent progression and development of metastases may be possible in the future and warrant study to pause progression of disease. Animal studies using lanreotide (Lopez et al 2019) and pasireotide (Quinn et al 2012, Walls et al 2016 After 6 years of follow-up, MRI revealed a liver lesion, while the pancreatic primaries remained unchanged. Subsequent 68 Gallium DOTATATE PET-CT scan showed liver and lymph node metastasis (A) as well as the small pancreatic primaries (B).…”

Section: Secondary Prevention Of Nf-pannets In Patients With Men1mentioning

confidence: 99%

HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: MEN1-related pancreatic NETs: identification of unmet clinical needs and future directives

Pieterman

Sadowski

Maxwell

et al. 2020

Endocrine-Related Cancer

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The PanNET Working Group of the 16th International Multiple Endocrine Neoplasia Workshop (MEN2019) convened in Houston, TX, USA, 27–29 March 2019 to discuss key unmet clinical needs related to PanNET in the context of MEN1, with a special focus on non-functioning (nf)-PanNETs. The participants represented a broad range of medical scientists as well as representatives from patient organizations, pharmaceutical industry and research societies. In a case-based approach, participants addressed early detection, surveillance, prognostic factors and management of localized and advanced disease. For each topic, after a review of current evidence, key unmet clinical needs and future research directives to make meaningful progress for MEN1 patients with nf-PanNETs were identified. International multi-institutional collaboration is needed for adequately sized studies and validation of findings in independent datasets. Collaboration between basic, translational and clinical scientists is paramount to establishing a translational science approach. In addition, bringing clinicians, scientists and patients together improves the prioritization of research goals, assures a patient-centered approach and maximizes patient involvement. It was concluded that collaboration, research infrastructure, methodologic and reporting rigor are essential to any translational science effort. The highest priority for nf-PanNETs in MEN1 syndrome are (1) the development of a data and biospecimen collection architecture that is uniform across all MEN1 centers, (2) unified strategies for diagnosis and follow-up of incident and prevalent nf-PanNETs, (3) non-invasive detection of individual nf-PanNETs that have an increased risk of metastasis, (4) chemoprevention clinical trials driven by basic research studies and (5) therapeutic targets for advanced disease based on biologically plausible mechanisms.

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Section: Secondary Prevention Of Nf-pannets In Patients With Men1mentioning

confidence: 99%

HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: MEN1-related pancreatic NETs: identification of unmet clinical needs and future directives

Pieterman

Sadowski

Maxwell

et al. 2020

Endocrine-Related Cancer

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“…Nevertheless, in a MEN1 -knockout (KO) mouse model, the somatostatin analogue lanreotide significantly delayed pNET progression. 7 In addition, a retrospective clinical study reported that long-acting repeatable octreotide appeared to retard pNET progression in a series of 40 MEN1-associated pNETs <2 cm, with an objective response rate of 10%. 8 Furthermore, in a prospective series of 42 patients from the same group, lanreotide autogel resulted in a significant increase in progression-free survival at a median follow-up of 73 months.…”

mentioning

confidence: 99%

A New Medical Therapy for Multiple Endocrine Neoplasia Type 1?

Boharoon¹,

Grossman²

2022

European Endocrinology

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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.

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