Editorial: Unveiling the complexity of neuroendocrine neoplasms: biomarkers, classification, and translational perspectives
Year: 2026
Type: editorial
Abstract: capture tumor evolution, biological subgroups, and prognostic heterogeneity, defining clinically relevant molecular classes of NENs. A second major theme is the shift toward clinically meaningful risk stratification. Although grade, stage, differentiation, and anatomical site remain essential prognostic factors in NENs, they do not fully capture disease complexity. The NUTRIGETNE study expands risk assessment in GEP-NENs by predicting malnutrition and sarcopenia [6], highlighting the relevance of nutritional status, muscle mass, and functional vulnerability for outcomes, treatment tolerance, quality of life, and long-term management. The same need for refined risk assessment emerges in functioning PanNETs such as insulinomas. The early prediction of malignancy using tumor size and biochemical markers addresses a clinically relevant problem: although most insulinomas behave indolently, the timely identification of aggressive potential remains challenging [7]. Combining anatomical and biochemical information may help distinguish patients who require closer surveillance and more individualized diagnostic pathways. Similarly, the recognition of bone metastases as a high-risk feature in metastatic NETs, particularly in NETs of unknown primary origin, highlights the prognostic relevance of disease distribution [8]. These studies suggest that risk stratification should increasingly integrate tumor biology, functional phenotype, disease burden, metastatic pattern, and host-related factors. The Research Topic highlights the biological and clinical determinants of NET development within specific tissue contexts. Type 1 gastric NETs associated with autoimmune atrophic gastritis exemplify the interplay between chronic inflammation, endocrine cell alterations, and the gastric microenvironment [9]. Integrating pathological context, host-related factors, and tumor biology may support individualized surveillance strategies and advance translational research. RWE is essential in rare tumors. The Italian Association for Neuroendocrine Tumors survey on pheochromocytomas and paragangliomas (PPGLs) reveals variability in diagnostic and clinical practice, highlighting the need for harmonization across centers [10]. RWE identifies gaps between guidelines, expert consensus, and daily practice, helping optimize biochemical testing, imaging, genetic assessment, multidisciplinary evaluation, and follow-up by assessing the implementation of classification and diagnostic principles in clinical settings. Collectively, this Research Topic highlights four converging directions in NEN research: biomarkerinformed classification incorporating tissue markers, receptor profiles, lineage factors, and nonconventional molecules [1][2][3]; molecular and epigenetic profiling to refine biological taxonomies [4,5]; prognostic stratification integrating grade, stage, nutritional status, biochemical phenotype, metastatic patterns, and disease-specific risk factors [6][7][8]; and translational models integrating pathology, molecular data, clinical phenotype, and RWE into reproducible, clinically applicable frameworks [9,10]. NEN complexity should be viewed as an opportunity for precision classification and individualized risk assessment. Future research should validate emerging biomarkers in large, well-annotated cohorts, integrate multi-omic data with histopathology, imaging, and clinical outcomes, develop robust predictive models, and harmonize diagnostic criteria across heterogeneous entities, supported by sustained multidisciplinary collaboration and patient-centered research networks. In conclusion, this Research Topic provides a timely synthesis of the evolving diagnostic, biological, and translational paradigms in NENs. The articles gathered here show that the future of NEN research lies in moving from fragmented descriptors toward integrated models of disease identity and risk. By combining morphology, biomarkers, molecular and epigenetic profiling, functional status, clinical phenotype, and RWE, the field can advance toward more precise classification, earlier recognition of aggressive behavior, and better-informed translational research.We sincerely thank all authors, reviewers, and the Frontiers editorial team for their valuable contributions to this Research Topic.
Source: Frontiers in Endocrinology
Authors: Anna La Salvia, Giuseppe Fanciulli
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
OpenAlex ID: W7224101129