MicroRNAs and Treatment with Somatostatin Analogs in Gastro- Entero-Pancreatic Neuroendocrine Neoplasms: Challenges in Personalized Medicine

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 steadyincrease in incidence and prevalence. Their effective management depends on early diagnosis, personalizedrisk stratification, and monitoring response to therapy. A crucial element is identifying accurate biomarkers topredict/monitor therapeutic responses, assess drug resistance, and quantify residual disease in a reproducibleand less invasive way. Taking into consideration their role in cell differentiation, cell proliferation, apoptosisand tumor development, microRNAs have gained interest as potential prognostic markers and treatmentresponse predictors in neuroendocrine neoplasms. This review is the first to summarize the available dataon 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 targetingphosphoinositide 3 kinase – protein kinase B 1 – mammalian target of rapamycin signaling pathway mightrepresent a promising biomarker with potential clinical benefit, but further research is required beforetheir eventual clinical application. Furthermore, the ambiguous molecular mechanisms of neuroendocrineproliferation and the undefined signaling pathway of somatostatin analogs should encourage future researchin this field that may lead to a different clinical approach to neuroendocrine disease.