Epigenetic changes in gastroenteropancreatic neuroendocrine tumours

Mapelli, Paola; Aboagye, Eric O.; Stebbing, Justin; Sharma, Rohini

doi:10.1038/onc.2014.379

Cited by 11 publications

(7 citation statements)

References 82 publications

(92 reference statements)

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“…66 The basis for interlesion heterogeneity to radiotheranostic drugs is incompletely understood; however, in NETs, heterogeneous expression of the SSTR2 cell-surface target is thought to be largely driven by epigenetic modifications. 67 This led to the newly opened clinical trial F I G U R E 4 Dual SRI-FDG PET scans. (A) A man aged 61 years with metastatic small bowel carcinoid, grade 2 (Ki67, 5%), and nodal liver and bone metastases, SSR > FDG (PETNET score, P2 [range, P0-P5]; see Mapelli et al 67 ).…”

Section: Theranostics Audit Trailmentioning

confidence: 99%

“…67 This led to the newly opened clinical trial F I G U R E 4 Dual SRI-FDG PET scans. (A) A man aged 61 years with metastatic small bowel carcinoid, grade 2 (Ki67, 5%), and nodal liver and bone metastases, SSR > FDG (PETNET score, P2 [range, P0-P5]; see Mapelli et al 67 ). (B) A woman aged 34 years with a high-grade (grade 3; Ki67, 30%) biliary tree NET, which is FDG-avid but SSR-negative (PETNET score, P5): maximum intensity projection, axial-fused, and axial PET imaging.…”

Section: Theranostics Audit Trailmentioning

confidence: 99%

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Radiotheranostics in oncology: Making precision medicine possible

Aboagye

Barwick

Haberkorn

2023

CA A Cancer J Clinicians

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A quintessential setting for precision medicine, theranostics refers to a rapidly evolving field of medicine in which disease is diagnosed followed by treatment of disease‐positive patients using tools for the therapy identical or similar to those used for the diagnosis. Against the backdrop of only‐treat‐when‐visualized, the goal is a high therapeutic index with efficacy markedly surpassing toxicity. Oncology leads the way in theranostics innovation, where the approach has become possible with the identification of unique proteins and other factors selectively expressed in cancer versus healthy tissue, advances in imaging technology able to report these tissue factors, and major understanding of targeting chemicals and nanodevices together with methods to attach labels or warheads for imaging and therapy. Radiotheranostics—using radiopharmaceuticals—is becoming routine in patients with prostate cancer and neuroendocrine tumors who express the proteins PSMA (prostate‐specific membrane antigen) and SSTR2 (somatostatin receptor 2), respectively, on their cancer. The palpable excitement in the field stems from the finding that a proportion of patients with large metastatic burden show complete and partial responses, and this outcome is catalyzing the search for more radiotheranostics approaches. Not every patient will benefit from radiotheranostics; but, for those who cross the target‐detected line, the likelihood of response is very high.

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Section: Theranostics Audit Trailmentioning

confidence: 99%

Section: Theranostics Audit Trailmentioning

confidence: 99%

Radiotheranostics in oncology: Making precision medicine possible

Aboagye

Barwick

Haberkorn

2023

CA A Cancer J Clinicians

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“…RASSF1A not only regulates cellular proliferation, but also influences apoptosis and stabilization of microtubules, and downregulation has been reported in many cancers, including GEP NETs and other cancers of neuroendocrine origin ( 51 – 55 , 64 ). Overexpression of RASSF1C occurs primarily in pNETs and is thought to inhibit beta-catenin within the Wnt signaling pathway, suggesting a role in development of pNETs ( 65 ).…”

Section: Dna Methylationmentioning

confidence: 99%

“…Histone deacetylases (HDACs) catalyze the removal of acetyl groups from specific lysine residues in histone proteins allowing for closing of chromatin and gene silencing. Histone acetyltransferases (HATs) do the opposite and mediate acetylation of histones resulting in a reduction in the positive charge on the surface of histones to loosen the attraction between DNA and the histones resulting in more open chromatin and gene accessibility for transcriptional activation ( 65 ).…”

Section: Chromatin Remodelingmentioning

confidence: 99%

Epigenetic Regulation in Gastroenteropancreatic Neuroendocrine Tumors

Crabtree

2022

Front. Oncol.

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Gastroenteropancreatic neuroendocrine neoplasms are a rare, diverse group of neuroendocrine tumors that form in the pancreatic and gastrointestinal tract, and often present with side effects due to hormone hypersecretion. The pathogenesis of these tumors is known to be linked to several genetic disorders, but sporadic tumors occur due to dysregulation of additional genes that regulate proliferation and metastasis, but also the epigenome. Epigenetic regulation in these tumors includes DNA methylation, chromatin remodeling and regulation by noncoding RNAs. Several large studies demonstrate the identification of epigenetic signatures that may serve as biomarkers, and others identify innovative, epigenetics-based targets that utilize both pharmacological and theranostic approaches towards the development of new treatment approaches.

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“…15 NETs demonstrate epigenetic changes such as promoter methylation and histone modifications; these factors may present targets for future therapeutic approaches. 16 Several genetic tumor syndromes predispose patients to the development of GI-NETs. Approximately 20% of NETs are related to these syndromes.…”

Section: Genetic Changesmentioning

confidence: 99%

Gastrointestinal Neuroendocrine Tumors: Clinical and Pathological Correlates

2019

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Gastrointestinal neuroendocrine tumors (GI-NETs), previously classified as carcinoid tumors, are rare cancers that arise from cells of the diffuse endocrine system of the gastrointestinal tract. These tumors most commonly arise from the bronchus, jejunoileum, or colon/rectum. They produce peptide products that can lead to identifiable clinical syndromes such as carcinoid syndrome, which is classically associated with diarrhea, flushing, and heart disease. The latest classifications of GI-NETs include pancreatic NETs, which can produce a wide range of pancreatic hormones leading to syndromes such as Zollinger–Ellison's syndrome. The prognosis for patients with GI-NETs varies widely depending on the size, location, and presence of metastatic disease, with 5-year survival rates ranging from 0 to 15% for poorly differentiated NETs and 10-year survival rates of up to 100% for patients with insulinomas smaller than 2 cm. A wide range of treatment modalities is commonly used to treat GI-NETs, including surgical and endoscopic resection, locoregional therapies, cytotoxic chemotherapy, and somatostatin receptor targeted therapy. The goal of this review is to detail the classification, epidemiology, clinical syndromes, diagnosis, and staging of these tumors and to provide an overview of management strategies.

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Epigenetic changes in gastroenteropancreatic neuroendocrine tumours

Cited by 11 publications

References 82 publications

Radiotheranostics in oncology: Making precision medicine possible

Radiotheranostics in oncology: Making precision medicine possible

Epigenetic Regulation in Gastroenteropancreatic Neuroendocrine Tumors

Gastrointestinal Neuroendocrine Tumors: Clinical and Pathological Correlates

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