Gastroenteropancreatic neuroendocrine neoplasms: genes, therapies and models

Area of Science:

• Oncology
• Gastroenterology
• Endocrinology
• Cancer Biology

Background:

• Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of cancers, including well-differentiated GEP-NETs and poorly differentiated GEP-NECs.
• The incidence of GEP-NENs is rising, emphasizing the need for better etiological understanding and treatment strategies.
• Limited patient numbers hinder large-scale clinical trials, necessitating the development of effective disease models.

Purpose of the Study:

• To review the current understanding of GEP-NEN genetics and biology.
• To compare conventional disease models (GEMMs, cell lines) with human GEP-NEN phenotypes.
• To highlight emerging models (patient-derived xenografts, organoids) for therapeutic insights.

Main Methods:

• Review of existing literature on GEP-NEN genetics and biology.
• Analysis of conventional disease models, including genetically engineered mouse models (GEMMs) and cell lines.
• Evaluation of emerging models derived from human clinical samples, such as patient-derived xenografts and organoids.

Main Results:

• Conventional models like GEMMs and cell lines offer insights but have phenotypic differences compared to human GEP-NENs.
• Emerging models, including patient-derived xenografts and organoids, show promise in reflecting human disease characteristics.
• These advanced models may provide crucial biological and therapeutic insights into GEP-NENs.

Conclusions:

• Tractable disease models are essential for advancing the study and treatment of GEP-NENs.
• Emerging models derived from human samples offer a more faithful representation of GEP-NENs.
• Further development and utilization of these models are critical for uncovering new therapeutic strategies.