Investigating Carcinoid Tumor Oncogenesis through the lens of Developmental Dynamics involved in Small Intestinal Neuroendocrine Cells

Abstract

Abstract Background: Carcinoid tumors from small intestinal Neuroendocrine Cells (SI-NECs) present clinical challenges with increasing incidence. Investigating the genetic architecture is crucial, as dysregulation in transcription factors and signaling pathways contributes to aberrant behavior, including uncontrolled proliferation and hormone secretion. Understanding these mechanisms holds promise for identifying therapeutic targets and biomarkers, not only for carcinoid tumors but also for broader applications in neuroendocrine neoplasms and gastrointestinal malignancies. Methods: Databases, including PubMed, MEDLINE, Google Scholar, and open access/subscription-based journals were searched for published articles without any date restrictions, to investigate the intricate genetic architecture and developmental dynamics underlying the development of carcinoid tumors originating from small intestinal Neuroendocrine Cells (SI-NECs). Based on the criteria mentioned in the methods section, studies were systematically reviewed to investigate carcinoid tumor oncogenesis. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Results: This investigation into the genetic architecture of small intestinal neuroendocrine cells (SI-NECs) reveals intricate dysregulations contributing to carcinoid tumor development. Dysfunctional expression of key transcription factors, including Neurogenin 3, Pdx1, Isl1, Foxa1/2, Hes1, and others, disrupts neuroendocrine differentiation, impacting hormone expression profiles. Chromogranin A dysregulation affects the maturation of SI-NECs, while alterations in Delta-like 1/4 and serotonin contribute to abnormal behavior. Dysfunctional Tcf4 and Gfi1b influence cell fate decisions, and NeuroD1 alterations impact maturation. Dysregulation of GATA factors, Nkx2.2, Sox factors, and Neurotrophins further complicates SI-NECs. Protein Kinase A signaling dysregulation contributes to uncontrolled proliferation. These findings advance our understanding of the complexity of carcinoid tumor development, possibly providing a framework for targeted therapeutic strategies addressing the specific aberrations identified in SI-NECs. Conclusion: The dysregulation in the genetic architecture of small intestinal Neuroendocrine Cells (SI-NECs) precipitates carcinoid tumor development. Alterations in key transcription factors, signaling pathways, and developmental processes disrupt neuroendocrine differentiation, hormone expression, and cell fate determination. Dysfunctional molecular cascades including Notch and Wnt signaling drive uncontrolled proliferation and aberrant hormone secretion characteristic of carcinoid tumors. Understanding the intricate molecular landscape of SI-NEC dysregulation is paramount for targeted therapies. Insights emerging from this research may pave the way for novel interventions aimed at mitigating carcinoid tumor progression and improving patient outcomes.