Animal models of spontaneous pancreatic neuroendocrine tumors

Yu, Run

doi:10.1016/j.mce.2015.08.004

Cited by 12 publications

(8 citation statements)

References 91 publications

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“…Accordingly, in animal models of either gastric or colorectal cancer, the mTOR inhibitor everolimus significantly decreased microvessel density, suggestive of a direct effect on the TME (Onoyama et al 2013, Yuge et al 2015. Major clinical trials have been published over the past few years with the use of mTOR inhibitor everolimus in the field of NETs with significant impact over the PFS of treated patients vs the placebo group , 2016, Pusceddu et al 2016.…”

Section: :11mentioning

confidence: 99%

“…An alternative way could be studies on primary cultures of human GEP-NETs tumor, representing an affordable and individualized approach of the tumor biology and response to treatment from bench to bedside (Mohamed et al 2017). Alternative options to optimally reproduce the in vivo landscape of the TME could be the use of microencapsulated SI-NET cells (Rokstad et al 2012), as well as the development of animal models of spontaneous PNETs could be a solution (Yu 2016). In addition, 3D spheroid culturing of NET cells (Wong et al 2012) or pheochromocytoma cells (D'Antongiovanni et al 2017), allowing cell-cell interactions, have been successfully performed and give the possibility to perform histological, immunohistochemical and functional analysis and takes into consideration the tumor and its microenvironment.…”

Section: Summarizing Conclusionmentioning

confidence: 99%

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Role of the tumor microenvironment in digestive neuroendocrine tumors

Cuny¹,

Herder²,

Barlier³

et al. 2018

Endocrine-Related Cancer

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Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a group of heterogeneous tumors whose incidence increased over the past few years. Around half of patients already present with metastatic disease at the initial diagnosis. Despite extensive efforts, cytotoxic and targeted therapies have provided only limited efficacy for patients with metastatic GEP-NETs, mainly due to the development of a certain state of resistance. One factor contributing to both the failure of systemic therapies and the emergence of an aggressive tumor phenotype may be the tumor microenvironment (TME), comprising dynamic and adaptative assortment of extracellular matrix components and non-neoplastic cells, which surround the tumor niche. Accumulating evidence shows that the TME can simultaneously support both tumor growth and metastasis and contribute to a certain state of resistance to treatment. In this review, we summarize the current knowledge of the TME of GEP-NETs and discuss the current therapeutic agents that target GEP-NETs and those that could be of interest in the (near) future.

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Section: :11mentioning

confidence: 99%

Section: Summarizing Conclusionmentioning

confidence: 99%

Role of the tumor microenvironment in digestive neuroendocrine tumors

Cuny¹,

Herder²,

Barlier³

et al. 2018

Endocrine-Related Cancer

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show abstract

“…Flanking lineage tracing experiments, in which the renin promoter construct controlled expression of fluorescent reporters, confirmed renin promoter activity in the developing pancreas and pinpointed α-cell precursors as likely cells of origin for glucagonoma formation. On the one hand, the model recapitulates human sporadic glucagonomas and may be useful for studying the response to targeted therapies [127, 128]. On the other hand, the underlying genetic alterations and the aggressive course recommend these mice as a model for pancreatic NEC [25].…”

Section: Models Of Gep-net and Gep-necmentioning

confidence: 99%

Models of Gastroenteropancreatic Neuroendocrine Neoplasms: Current Status and Future Directions

et al. 2020

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Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a rare, heterogeneous group of tumors that originate from the endocrine system of the gastrointestinal tract and pancreas. GEP-NENs are subdivided according to their differentiation into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Since GEP-NENs represent rare diseases, only limited data from large prospective, randomized clinical trials are available, and recommendations for treatment of GEP-NEN are in part based on data from retrospective analyses or case series. In this context, tractable disease models that reflect the situation in humans and that allow to recapitulate the different clinical aspects and disease stages of GEP-NET or GEP-NEC are urgently needed. In this review, we highlight available data on mouse models for GEP-NEN. We discuss how these models reflect tumor biology of human disease and whether these models could serve as a tool for understanding the pathogenesis of GEP-NEN and for disease modeling and pharmacosensitivity assays, facilitating prediction of treatment response in patients. In addition, open issues applicable for future developments will be discussed.

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“…Preclinical models of NETs currently encompass only a limited number of human NET cell lines and mouse models, as has been recently reviewed ( 21 , 22 , 23 , 24 ). The most commonly used human neuroendocrine neoplasia cell lines of GEP origin encompass the pancreatic cell lines BON1 ( 25 ) and QGP1 ( 26 ), as well as the small intestinal cell lines GOT1 ( 27 ) and KRJ-I ( 28 ).…”

Section: Novel Targets and Future Strategies In Netsmentioning

confidence: 99%

Targeted therapy of gastroenteropancreatic neuroendocrine tumours: preclinical strategies and future targets

Prada

Auernhammer

2018

Endocrine Connections

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Molecular targeted therapy of advanced neuroendocrine tumours (NETs) of the gastroenteropancreatic (GEP) system currently encompasses approved therapy with the mammalian target of rapamycin (mTOR) inhibitor everolimus and the multi-tyrosinkinase inhibitor sunitinib. However, clinical efficacy of these treatment strategies is limited by low objective response rates and limited progression-free survival due to tumour resistance. Further novel strategies for molecular targeted therapy of NETs of the GEP system are needed. This paper reviews preclinical research models and signalling pathways in NETs of the GEP system. Preclinical and early clinical data on putative novel targets for molecular targeted therapy of NETs of the GEP system are discussed, including PI3K, Akt, mTORC1/mTORC2, GSK3, c-Met, Ras–Raf–MEK–ERK, embryogenic pathways (Hedgehog, Notch, Wnt/beta-catenin, TGF-beta signalling and SMAD proteins), tumour suppressors and cell cycle regulators (p53, cyclin-dependent kinases (CDKs) CDK4/6, CDK inhibitor p27, retinoblastoma protein (Rb)), heat shock protein HSP90, Aurora kinase, Src kinase family, focal adhesion kinase and epigenetic modulation by histone deacetylase inhibitors.

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Animal models of spontaneous pancreatic neuroendocrine tumors

Cited by 12 publications

References 91 publications

Role of the tumor microenvironment in digestive neuroendocrine tumors

Role of the tumor microenvironment in digestive neuroendocrine tumors

Models of Gastroenteropancreatic Neuroendocrine Neoplasms: Current Status and Future Directions

Targeted therapy of gastroenteropancreatic neuroendocrine tumours: preclinical strategies and future targets

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