Current and New Challenges in the Management of Pancreatic Neuroendocrine Tumors: The Role of miRNA-Based Approaches as New Reliable Biomarkers

Abstract

Pancreatic neuroendocrine tumors (PanNETs) are rare tumors; however, their incidence greatly increases with age, and they occur more frequently among the elderly. They represent 5% of all pancreatic tumors, and despite the fact that low-grade tumors often have an indolent evolution, they portend a poor prognosis in an advanced stages and undifferentiated tumors. Additionally, functional pancreatic neuroendocrine tumors greatly impact quality of life due to the various clinical syndromes that result from abnormal hormonal secretion. With limited therapeutic and diagnostic options, patient stratification and selection of optimal therapeutic strategies should be the main focus. Modest improvements in the management of pancreatic neuroendocrine tumors have been achieved in the last years. Therefore, it is imperative to find new biomarkers and therapeutic strategies to improve patient survival and quality of life, limiting the disease burden. MicroRNAs (miRNAs) are small endogenous molecules that modulate the expression of thousands of genes and control numerous critical processes involved in tumor development and progression. New data also suggest the implication of miRNAs in treatment resistance and their potential as prognostic or diagnostic biomarkers and therapeutic targets. In this review, we discusses the current and new challenges in the management of PanNETs, including genetic and epigenetic approaches. Furthermore, we summarize the available data on miRNAs as potential prognostic, predictive, or diagnostic biomarkers and discuss their function as future therapeutic targets.

Epigenetic Regulation in Gastroenteropancreatic Neuroendocrine Tumors

“…Klieser identified a “proliferative” miRNA signature that correlated with expression of HDAC as well as staging, grade and hormone activity in pNETs ( 120 ). Taken together, these data confirm much of the previous work focused on selected miRNAs such as miR-24 ( 121 , 122 ), miR-21 ( 123 ), and others as reviewed recently ( 9 ) and is a critical step towards understanding the prognostic and diagnostic role of miRNAs.…”

“…Several miRNA profiling studies have been performed on NENs towards the goal of identifying miRNAs that hold promise as biomarkers to distinguish between the different tissues of origin within GEP-NENs as well as pancreatic acinar cell carcinoma ( 9 , 117 , 118 ). One case report analyzed the miRNA signature of normal pancreas, gastrinoma and pNET from a single MEN1 patient and highlighted sets of miRNAs that fall into two gene regulatory networks with distinct functional features ( 119 ).…”

Exploring the theranostic potentials of miRNA and epigenetic networks in autoimmune diseases: A comprehensive review

“…The miRNA drug is easily degraded in the first pass metabolism due to the action of nuclease on the miRNA. A possible concern may arise if the miRNA is used in a higher dose to surpass the degradation quotient, leading to unwanted side effects 227 . They may cause cross reactivity in various pathologies or may aggravate a particular stage of a disease.…”

“…A possible concern may arise if the miRNA is used in a higher dose to surpass the degradation quotient, leading to unwanted side effects. 227 They may cause cross reactivity in various pathologies or may aggravate a particular stage of a disease. The miRNA biomarker detection and reproducibility are a cumbersome process.…”

Towards Personalized Treatment and Molecular Research on Gastrointestinal Tumors

“…In the review by Havasi and collaborators the state of the art and future perspectives in the management of pNETs are analyzed, including genetic and epigenetic approaches. In particular, authors focused on miRNAs as potential prognostic, predictive, or diagnostic biomarkers and discussed their function as future therapeutic targets [ 5 ].…”