Abstract

Molecular predictive biomarkers represent an essential tool for the future of personalized oncotherapy. Gastro-
entero-pancreatic neuroendocrine neoplasms are a heterogeneous group of epithelial tumors with a steady
increase in incidence and prevalence. Their effective management depends on early diagnosis, personalized
risk stratification, and monitoring response to therapy. A crucial element is identifying accurate biomarkers to
predict/monitor therapeutic responses, assess drug resistance, and quantify residual disease in a reproducible
and less invasive way. Taking into consideration their role in cell differentiation, cell proliferation, apoptosis
and tumor development, microRNAs have gained interest as potential prognostic markers and treatment
response predictors in neuroendocrine neoplasms. This review is the first to summarize the available data
on the possible role of microRNAs in evaluating the efficacy of somatostatin analogs treatment in gastro-
entero-pancreatic neuroendocrine neoplasms. Although the literature is scarce, the let-7 family targeting
phosphoinositide 3 kinase – protein kinase B 1 – mammalian target of rapamycin signaling pathway might
represent a promising biomarker with potential clinical benefit, but further research is required before
their eventual clinical application. Furthermore, the ambiguous molecular mechanisms of neuroendocrine
proliferation and the undefined signaling pathway of somatostatin analogs should encourage future research
in this field that may lead to a different clinical approach to neuroendocrine disease.

Keywords

neuroendocrine neoplasms, somatostatin analogs, microRNAs, predictive biomarkers, let-7 family