Lineage plasticity and histological transformation: tumor histology as a spectrum.

IF 25.9 1区 生物学 Q1 CELL BIOLOGY
Xiaoling Li,Eric E Gardner,Sonia Molina-Pinelo,Clare Wilhelm,Ping Mu,Álvaro Quintanal-Villalonga
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引用次数: 0

Abstract

Lineage plasticity, the ability of cells to transition to an alternative phenotype as a means for adaptation, is an increasingly recognized mechanism of tumor evolution and a driver of resistance to anticancer therapies. The most extensively described clinical settings impacted by such molecular phenomena include neuroendocrine transformation in androgen receptor-dependent prostate adenocarcinoma, and adenocarcinoma-to-neuroendocrine and adenocarcinoma-to-squamous transdifferentiation in epidermal growth factor receptor-driven lung adenocarcinoma, affecting 10%-20% of patients treated with targeted therapy. Recent analyses of human tumor samples and in vivo models of histological transformation have led to insights into the biology of lineage plasticity, including biomarkers predictive of high risk of transformation. However, no clinically available therapies aimed to prevent or revert plasticity are currently available. In the present review, we will provide a biological and therapeutic overview of the current understanding of common and divergent molecular drivers of neuroendocrine and squamous transdifferentiation in tumors from different origins, including descriptive analysis of previously known and recently described molecular events associated with histological transformation, and propose evidence-based alternative models of transdifferentiation. A clear definition of the commonalities and differences of transforming tumors in different organs and to different histological fates will be important to translate molecular findings to the clinical setting.
谱系可塑性和组织学转化:肿瘤组织学作为一个光谱。
谱系可塑性,即细胞向另一种表型转变的能力,作为一种适应手段,是肿瘤进化的一种日益被认可的机制,也是对抗癌治疗产生耐药性的驱动因素。受这种分子现象影响的最广泛描述的临床情况包括雄激素受体依赖性前列腺癌的神经内分泌转化,以及表皮生长因子受体驱动的肺腺癌的腺癌向神经内分泌和腺癌向鳞状细胞的转分化,影响10%-20%接受靶向治疗的患者。最近对人类肿瘤样本和体内组织学转化模型的分析已经导致对谱系可塑性生物学的深入了解,包括预测转化高风险的生物标志物。然而,目前临床上还没有旨在预防或恢复可塑性的治疗方法。在目前的综述中,我们将对不同来源的肿瘤中神经内分泌和鳞状细胞转分化的共同和不同的分子驱动因素进行生物学和治疗方面的概述,包括对先前已知和最近描述的与组织学转化相关的分子事件的描述性分析,并提出基于证据的转分化替代模型。明确定义不同器官和不同组织学命运的转化性肿瘤的共性和差异对于将分子发现转化为临床环境至关重要。
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
Cell Research
Cell Research 生物-细胞生物学
CiteScore
53.90
自引率
0.70%
发文量
2420
审稿时长
2.3 months
期刊介绍: Cell Research (CR) is an international journal published by Springer Nature in partnership with the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CAS). It focuses on publishing original research articles and reviews in various areas of life sciences, particularly those related to molecular and cell biology. The journal covers a broad range of topics including cell growth, differentiation, and apoptosis; signal transduction; stem cell biology and development; chromatin, epigenetics, and transcription; RNA biology; structural and molecular biology; cancer biology and metabolism; immunity and molecular pathogenesis; molecular and cellular neuroscience; plant molecular and cell biology; and omics, system biology, and synthetic biology. CR is recognized as China's best international journal in life sciences and is part of Springer Nature's prestigious family of Molecular Cell Biology journals.
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