Molecular Subtypes of Neuroendocrine Carcinoma: From Chaos to Consensus.

IF 34.5 1区医学 Q1 PATHOLOGY

Annual Review of Pathology-Mechanisms of Disease Pub Date : 2025-10-08 DOI:10.1146/annurev-pathmechdis-042524-023153

Zhanyu Wang,Nan Sun,Jie He,Esther Redin,Charles M Rudin

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引用次数: 0

Abstract

Neuroendocrine carcinomas (NECs) represent a notoriously aggressive family of lethal malignancies arising across diverse anatomical sites. Molecular subtyping based on key transcription factors ASCL1, NEUROD1, POU2F3, and YAP1 has significantly advanced understanding of tumor heterogeneity in small cell lung cancer (SCLC). Beyond SCLC, extrapulmonary NECs demonstrate analogous heterogeneity, similarly governed by these transcriptional determinants. Recent studies have further identified a fifth subtype driven by the lineage-specifying factor HNF4A. This review aims to propose a unified pan-NEC classification framework for consistent molecular subtyping across pulmonary, gastro-entero-pancreatic (GEP), and genitourinary systems. We delineate the distinct lineage hallmarks of the ANHPY subtypes (neuroendocrine, neuronal, GEP-like, tuft-like, and epithelial-mesenchymal transition phenotypes) and explore their connections to defining mechanisms, genetic alterations, clinicopathological features, and therapeutic vulnerabilities. This unified framework serves as a molecular roadmap for precise NEC research and management.

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神经内分泌癌的分子亚型：从混乱到一致。

神经内分泌癌（NECs）是一种非常具有侵略性的致命恶性肿瘤，发生在不同的解剖部位。基于关键转录因子ASCL1、NEUROD1、POU2F3和YAP1的分子分型可以显著提高对小细胞肺癌（SCLC）肿瘤异质性的认识。除SCLC外，肺外NECs也表现出类似的异质性，同样受这些转录决定因素的支配。最近的研究进一步确定了由谱系指定因子HNF4A驱动的第五种亚型。本综述旨在提出一个统一的泛nec分类框架，以便在肺、胃肠胰腺（GEP）和泌尿生殖系统中进行一致的分子分型。我们描述了ANHPY亚型（神经内分泌型、神经元型、gep样型、簇样型和上皮-间质转化表型）的独特谱系特征，并探讨了它们与定义机制、遗传改变、临床病理特征和治疗脆弱性的联系。这个统一的框架作为精确的NEC研究和管理的分子路线图。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annual Review of Pathology-Mechanisms of Disease 医学-病理学

CiteScore

62.60

自引率

0.00%

发文量

期刊介绍： The Annual Review of Pathology: Mechanisms of Disease is a scholarly journal that has been published since 2006. Its primary focus is to provide a comprehensive overview of recent advancements in our knowledge of the causes and development of significant human diseases. The journal places particular emphasis on exploring the current and evolving concepts of disease pathogenesis, as well as the molecular genetic and morphological changes associated with various diseases. Additionally, the journal addresses the clinical significance of these findings. In order to increase accessibility and promote the broad dissemination of research, the current volume of the journal has transitioned from a gated subscription model to an open access format. This change has been made possible through the Annual Reviews' Subscribe to Open program, which allows all articles published in this volume to be freely accessible to readers. As part of this transition, all articles in the journal are published under a Creative Commons Attribution (CC BY) license, which encourages open sharing and use of the research.