The molecular biology of pancreatic neuroendocrine neoplasms: Challenges and translational opportunities

Young, Kate; Starling, Naureen; Sadanandam, Anguraj

doi:10.1016/j.semcancer.2019.09.024

Cited by 14 publications

(8 citation statements)

References 70 publications

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“…Before the last decade genetic studies on molecular alterations of GEP-NENs were limited and mainly based on data from genetic syndromes associated with endocrine neoplasms. The diffusion and fruition of next-generation sequencing and other high-throughput techniques (microarray expression, miRNAs, and methylome analyses) in recent years have provided a larger amount of genetic and epigenetic information and a wider view of these malignancies, and especially of PanNENs, from a genetic perspective as reviewed in a very comprehensive manner by several authors (119,(123)(124)(125)(126)(127)(128)(129)(130).…”

Section: Genetic Alterations Promoting Nen Developmentmentioning

confidence: 99%

Biomarkers for Pancreatic Neuroendocrine Neoplasms (PanNENs) Management—An Updated Review

et al. 2020

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Pancreatic neuroendocrine tumors (PanNENs) are rare sporadic cancers or develop as part of hereditary syndromes. PanNENs can be both functioning and non-functioning based on whether they produce bioactive peptides. Some PanNENs are well differentiated while others-poorly. Symptoms, thus, depend on both oncological and hormonal causes. PanNEN diagnosis and treatment benefit from and in some instances are guided by biomarker monitoring. However, plasmatic monoanalytes are only suggestive of PanNEN pathological status and their positivity is typically followed by deepen diagnostic analyses through imaging techniques. There is a strong need for new biomarkers and follow-up modalities aimed to improve the outcome of PanNEN patients. Liquid biopsy follow-up, i.e., sequential analysis on tumor biomarkers in body fluids offers a great potential, that need to be substantiated by additional studies focusing on the specific markers and the timing of the analyses. This review provides the most updated panorama on PanNEN biomarkers.

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Section: Genetic Alterations Promoting Nen Developmentmentioning

confidence: 99%

Biomarkers for Pancreatic Neuroendocrine Neoplasms (PanNENs) Management—An Updated Review

et al. 2020

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“…BON-1 and QGP-1 cells were recently authenticated to belong to neuroendocrine and epithelial lineage, but their molecular characterizations do not often resemble those seen in patients’ primary cancers. For instance, exome sequencing and genome-wide copy number analysis reveal that BON-1 and QGP-1 do not harbor PNET-associated mutations such as mTOR, DAXX/ATRX, MEN1, VHL, and NF; questioning the relevance of using these models for PNET study[ 94 , 95 ]. The fast growing potential of these two cell lines does not reflect the slow growth phenotype of most PNETs[ 96 ].…”

Section: Pnets Lack Sizable Number Of Pre-clinical Cellular Modelsmentioning

confidence: 99%

Pancreatic neuroendocrine tumors: Therapeutic challenges and research limitations

Mpilla

Philip

El‐Rayes

et al. 2020

WJG

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Pancreatic neuroendocrine tumors (PNETs) are known to be the second most common epithelial malignancy of the pancreas. PNETs can be listed among the slowest growing as well as the fastest growing human cancers. The prevalence of PNETs is deceptively low; however, its incidence has significantly increased over the past decades. According to the American Cancer Society’s estimate, about 4032 (> 7% of all pancreatic malignancies) individuals will be diagnosed with PNETs in 2020. PNETs often cause severe morbidity due to excessive secretion of hormones (such as serotonin) and/or overall tumor mass. Patients can live for many years (except for those patients with poorly differentiated G3 neuroendocrine tumors); thus, the prevalence of the tumors that is the number of patients actually dealing with the disease at any given time is fairly high because the survival is much longer than pancreatic ductal adenocarcinoma. Due to significant heterogeneity, the management of PNETs is very complex and remains an unmet clinical challenge. In terms of research studies, modest improvements have been made over the past decades in the identification of potential oncogenic drivers in order to enhance the quality of life and increase survival for this growing population of patients. Unfortunately, the majority of systematic therapies approved for the management of advanced stage PNETs lack objective response or at most result in modest benefits in survival. In this review, we aim to discuss the broad challenges associated with the management and the study of PNETs.

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“…First‐line therapies for these metastatic tumors varied widely, indicating current lack of clinical consensus for treatment of NET subgroups. The identification of active drugs in GEP‐NETs remains limited in part by the lack of validated molecular markers for risk stratification 34–36 . Strategies such as blood‐based biomarkers and assessment of radiomic imaging features also hold promise for assessing interpatient heterogeneity and have the appeal of using data from a single time point 37–41 .…”

Section: Discussionmentioning

confidence: 99%

“…The identification of active drugs in GEP-NETs remains limited in part by the lack of validated molecular markers for risk stratification. [34][35][36] Strategies such as blood-based biomarkers and assessment of radiomic imaging features also hold promise for assessing interpatient heterogeneity and have the appeal of using data from a single time point. [37][38][39][40][41] When feasible to acquire two pretreatment scans, documenting TGR 0 could enhance our ability to non-invasively identify treatment-naïve patients at greatest risk for future grade progression and change in Ki67 over time.…”

Section: G3mentioning

confidence: 99%

Baseline tumor growth rate highlights the heterogeneity of well differentiated gastroenteropancreatic neuroendocrine tumors and predicts for increases in Ki67 index over time

Wang

Whitman

Paciorek

et al. 2023

J Neuroendocrinology

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Refined risk stratification for gastroenteropancreatic neuroendocrine tumors (GEP‐NETs) has the potential to improve comparisons of study populations across clinical trials and facilitate drug development. Tumor growth rate (TGR) is a radiological metric with demonstrated prognostic value in well differentiated grade 1 and 2 (G1–2) GEP‐NETs, but little is known about TGR in G3 NETs. In this retrospective study of 48 patients with advanced G1–3 GEP‐NET, we calculated baseline TGR (TGR0) from radiological images of metastases acquired prior to first‐line therapy and evaluated its association with disease characteristics and outcomes. The median pretreatment Ki67 proliferation index for G1–3 tumors combined was 5% (range = 0.1%–52%) and median TGR0 was 4.8%/month (m) (range = 0%–45.9%/m). TGR0 correlated with pretreatment Ki67 across G1–3 pooled and within G3 GEP‐NET. Patients with higher TGR0 (>11.7%/m) tumors, which were primarily G3 pancreatic NETs, exhibited decreased time to first therapy (median, 2.2 vs. 5.3 months; p = .03) and shorter overall survival (median, 4.1 years vs. not reached; p = .003). Independent of therapies given, higher TGR0 GEP‐NETs experienced a greater incidence of Ki67 increase (100 vs. 50%; p = .02) and greater magnitude of Ki67 change (median, 14.0 vs. 0.1%; p = .04) upon serial biopsy. Importantly, TGR0, but not grade, predicted for future Ki67 increase in this series. Given the heterogeneity of well differentiated GEP‐NETs, future clinical trials may benefit from stratification for TGR0, particularly in G1–2 tumors, in which TGR0 does not correlate with Ki67. TGR0 has the potential to noninvasively identify patients with previously undiagnosed grade progression and those in whom more or less frequent monitoring may be appropriate. Additional research is needed to determine the prognostic and predictive value of TGR0 in larger and more homogeneously treated cohorts, and to ascertain if post‐treatment TGR has value in previously treated patients starting a new line of therapy.

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The molecular biology of pancreatic neuroendocrine neoplasms: Challenges and translational opportunities

Cited by 14 publications

References 70 publications

Biomarkers for Pancreatic Neuroendocrine Neoplasms (PanNENs) Management—An Updated Review

Biomarkers for Pancreatic Neuroendocrine Neoplasms (PanNENs) Management—An Updated Review

Pancreatic neuroendocrine tumors: Therapeutic challenges and research limitations

Baseline tumor growth rate highlights the heterogeneity of well differentiated gastroenteropancreatic neuroendocrine tumors and predicts for increases in Ki67 index over time

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