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弥合乳腺癌休眠的差距:模型、机制及转化挑战

Bridging the Gap in Breast Cancer Dormancy: Models, Mechanisms, and Translational Challenges.

作者信息

Sabit Hussein, Abdel-Ghany Shaimaa, Albrahim Yasser, Wadan Al-Hassan Soliman, Rashwan Sanaa, Arneth Rebekka, Arneth Borros

机构信息

Department of Medical Biotechnology, College of Biotechnology, Misr University for Science and Technology, P.O. Box 77, Giza 3237101, Egypt.

Department of Environmental Biotechnology, College of Biotechnology, Misr University for Science and Technology, P.O. Box 77, Giza 3237101, Egypt.

出版信息

Pharmaceuticals (Basel). 2025 Jun 26;18(7):961. doi: 10.3390/ph18070961.


DOI:10.3390/ph18070961
PMID:40732251
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12298558/
Abstract

Breast cancer (BC) poses a significant clinical challenge due to late metastatic recurrence, driven by dormant disseminated tumor cells (DTCs). This review emphasizes the urgency of addressing tumor dormancy to reduce metastatic relapse, a major contributor to BC mortality. DTCs evade conventional therapies and immune surveillance, reactivating unpredictably, thus necessitating targeted strategies. Current research is fragmented, with conflicting data, inadequate models, and a lack of biomarkers hindering progress. This review synthesizes these gaps and proposes actionable priorities, advocating for integrated, standardized approaches. It highlights the roles of single-cell multi-omics, spatial transcriptomics, and humanized long-term models in unraveling dormancy mechanisms. The review also emphasizes macrophage-targeted therapies, dormancy-specific trials, and biomarker validation, offering paths to clinical translation. Ultimately, this work emphasizes the urgent need for integrated multi-omics approaches, including single-cell and spatial transcriptomics, combined with advanced computational analysis. Moreover, this review critically analyzes the existing research landscape, meticulously identifying key gaps, and proposing concrete, forward-looking directions for both fundamental research and clinical translation in the challenging field of BC dormancy.

摘要

由于休眠的播散肿瘤细胞(DTCs)导致晚期转移性复发,乳腺癌(BC)构成了重大的临床挑战。本综述强调了解决肿瘤休眠以减少转移性复发的紧迫性,转移性复发是BC死亡率的主要促成因素。DTCs逃避传统疗法和免疫监视,不可预测地重新激活,因此需要有针对性的策略。目前的研究零散,数据相互矛盾,模型不完善,缺乏生物标志物阻碍了进展。本综述综合了这些差距并提出了可行的优先事项,倡导采用综合、标准化的方法。它强调了单细胞多组学、空间转录组学和人源化长期模型在揭示休眠机制中的作用。该综述还强调了针对巨噬细胞的疗法、针对休眠的试验和生物标志物验证,为临床转化提供了途径。最终,这项工作强调了迫切需要综合多组学方法,包括单细胞和空间转录组学,并结合先进的计算分析。此外,本综述批判性地分析了现有的研究状况,精心识别关键差距,并为BC休眠这一具有挑战性的领域中的基础研究和临床转化提出了具体的前瞻性方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e419/12298558/9d37ec8e391a/pharmaceuticals-18-00961-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e419/12298558/642c000afe48/pharmaceuticals-18-00961-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e419/12298558/5ff0ef4d0d01/pharmaceuticals-18-00961-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e419/12298558/1b4471d15db6/pharmaceuticals-18-00961-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e419/12298558/e24b0f3a825c/pharmaceuticals-18-00961-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e419/12298558/9d37ec8e391a/pharmaceuticals-18-00961-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e419/12298558/642c000afe48/pharmaceuticals-18-00961-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e419/12298558/5ff0ef4d0d01/pharmaceuticals-18-00961-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e419/12298558/1b4471d15db6/pharmaceuticals-18-00961-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e419/12298558/e24b0f3a825c/pharmaceuticals-18-00961-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e419/12298558/9d37ec8e391a/pharmaceuticals-18-00961-g005.jpg

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本文引用的文献

[1]
Targeting the Dependence on PIK3C3-mTORC1 Signaling in Dormancy-Prone Breast Cancer Cells Blunts Metastasis Initiation.

Cancer Res. 2025-6-16

[2]
Anti-Tumour Immunity Relies on Targeting Tissue Homeostasis Through Monocyte-Driven Responses Rather Than Direct Tumour Cytotoxicity.

Liver Int. 2025-5

[3]
Re-epithelialization of cancer cells increases autophagy and DNA damage: Implications for breast cancer dormancy and relapse.

Sci Signal. 2025-4-22

[4]
Spatially resolved atlas of breast cancer uncovers intercellular machinery of venular niche governing lymphocyte extravasation.

Nat Commun. 2025-4-9

[5]
The impact of a high fat diet and platelet activation on pre-metastatic niche formation.

Nat Commun. 2025-4-2

[6]
The Combined Assessment of CTC and Status in Liquid Biopsy Samples Enhances the Clinical Value of Prediction in Metastatic Breast Cancer.

Int J Mol Sci. 2025-2-26

[7]
Integrating model systems and genomic insights to decipher mechanisms of cancer metastasis.

Nat Rev Genet. 2025-3-10

[8]
Enabling sensitive and precise detection of ctDNA through somatic copy number aberrations in breast cancer.

NPJ Breast Cancer. 2025-3-8

[9]
How modulation of the tumor microenvironment drives cancer immune escape dynamics.

Sci Rep. 2025-3-1

[10]
Epigenetic drugs in cancer therapy.

Cancer Metastasis Rev. 2025-2-26

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