The EstroGene2.0 database for endocrine therapy response and resistance in breast cancer.

IF 6.5 2区医学 Q1 ONCOLOGY

NPJ Breast Cancer Pub Date : 2024-12-19 DOI:10.1038/s41523-024-00709-4

Zheqi Li, Fangyuan Chen, Li Chen, Jiebin Liu, Danielle Tseng, Fazal Hadi, Soleilmane Omarjee, Kamal Kishore, Joshua Kent, Joanna Kirkpatrick, Clive D'Santos, Mandy Lawson, Jason Gertz, Matthew J Sikora, Donald P McDonnell, Jason S Carroll, Kornelia Polyak, Steffi Oesterreich, Adrian V Lee

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引用次数: 0

Abstract

Endocrine therapies targeting the estrogen receptor (ER/ESR1) are the cornerstone to treat ER-positive breast cancers patients, but resistance often limits their effectiveness. Notable progress has been made although the fragmented way data is reported has reduced their potential impact. Here, we introduce EstroGene2.0, an expanded database of its precursor 1.0 version. EstroGene2.0 focusses on response and resistance to endocrine therapies in breast cancer models. Incorporating multi-omic profiling of 361 experiments from 212 studies across 28 cell lines, a user-friendly browser offers comprehensive data visualization and metadata mining capabilities ( https://estrogeneii.web.app/ ). Taking advantage of the harmonized data collection, our follow-up meta-analysis revealed transcriptomic landscape and substantial diversity in response to different classes of ER modulators. Endocrine-resistant models exhibit a spectrum of transcriptomic alterations including a contra-directional shift in ER and interferon signalings, which is recapitulated clinically. Dissecting multiple ESR1-mutant cell models revealed the different clinical relevance of cell model engineering and identified high-confidence mutant-ER targets, such as NPY1R. These examples demonstrate how EstroGene2.0 helps investigate breast cancer's response to endocrine therapies and explore resistance mechanisms.

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乳腺癌内分泌治疗反应和耐药的EstroGene2.0数据库。

针对雌激素受体（ER/ESR1）的内分泌疗法是治疗ER阳性乳腺癌患者的基础，但耐药性往往限制了其有效性。尽管报告数据的分散方式降低了其潜在影响，但仍取得了显著进展。在这里，我们介绍EstroGene2.0，这是其前身1.0版本的扩展数据库。EstroGene2.0关注乳腺癌模型对内分泌治疗的反应和抵抗。结合28个细胞系的212项研究中的361项实验的多组学分析，用户友好的浏览器提供全面的数据可视化和元数据挖掘功能（https://estrogeneii.web.app/）。利用统一的数据收集，我们的后续荟萃分析揭示了转录组景观和对不同类型内质网调节剂的响应的实质性多样性。内分泌耐药模型表现出一系列转录组改变，包括内质网和干扰素信号的反向转移，这在临床上得到了概括。解剖多个esr1突变细胞模型揭示了细胞模型工程的不同临床相关性，并确定了高置信度的突变er靶点，如NPY1R。这些例子展示了EstroGene2.0如何帮助研究乳腺癌对内分泌治疗的反应并探索耐药机制。

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

NPJ Breast Cancer Medicine-Pharmacology (medical)

CiteScore

10.10

自引率

1.70%

发文量

122

审稿时长

9 weeks

期刊介绍： npj Breast Cancer publishes original research articles, reviews, brief correspondence, meeting reports, editorial summaries and hypothesis generating observations which could be unexplained or preliminary findings from experiments, novel ideas, or the framing of new questions that need to be solved. Featured topics of the journal include imaging, immunotherapy, molecular classification of disease, mechanism-based therapies largely targeting signal transduction pathways, carcinogenesis including hereditary susceptibility and molecular epidemiology, survivorship issues including long-term toxicities of treatment and secondary neoplasm occurrence, the biophysics of cancer, mechanisms of metastasis and their perturbation, and studies of the tumor microenvironment.