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骨髓中的前列腺癌休眠与再激活

Prostate Cancer Dormancy and Reactivation in Bone Marrow.

作者信息

Singh Deepak K, Patel Vaibhav G, Oh William K, Aguirre-Ghiso Julio A

机构信息

Division of Hematology and Oncology, Department of Medicine, Department of Otolaryngology, Department of Oncological Sciences, Tisch Cancer Institute, Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Division of Hematology and Oncology, Department of Medicine, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

出版信息

J Clin Med. 2021 Jun 16;10(12):2648. doi: 10.3390/jcm10122648.

Abstract

Prostate cancer has a variable clinical course, ranging from curable local disease to lethal metastatic spread. Eradicating metastatic cells is a unique challenge that is rarely met with the available therapies. Thus, targeting prostate cancer cells in earlier disease states is a crucial window of opportunity. Interestingly, cancer cells migrate from their primary site during pre-cancerous and malignant phases to seed secondary organs. These cells, known as disseminated cancer cells (DCCs), may remain dormant for months or decades before activating to form metastases. Bone marrow, a dormancy-permissive site, is the major organ for housed DCCs and eventual metastases in prostate cancer. The dynamic interplay between DCCs and the primary tumor microenvironment (TME), as well as that between DCCs and the secondary organ niche, controls the conversion between states of dormancy and activation. Here, we discuss recent discoveries that have improved our understanding of dormancy signaling and the role of the TME in modulating the epigenetic reprogramming of DCCs. We offer potential strategies to target DCCs in prostate cancer.

摘要

前列腺癌具有多变的临床病程,从可治愈的局部疾病到致命的转移性扩散。根除转移性细胞是一项独特的挑战,现有疗法很少能应对这一挑战。因此,在疾病早期阶段靶向前列腺癌细胞是一个关键的机会窗口。有趣的是,癌细胞在癌前和恶性阶段会从其原发部位迁移,以播种到继发器官。这些细胞被称为播散癌细胞(DCCs),在激活形成转移灶之前可能会休眠数月或数十年。骨髓是一个允许休眠的部位,是前列腺癌中容纳DCCs和最终转移灶的主要器官。DCCs与原发性肿瘤微环境(TME)之间以及DCCs与继发器官微环境之间的动态相互作用,控制着休眠状态和激活状态之间的转换。在这里,我们讨论了最近的发现,这些发现增进了我们对休眠信号以及TME在调节DCCs表观遗传重编程中的作用的理解。我们提供了在前列腺癌中靶向DCCs的潜在策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/da8c/8234151/676b1886d65a/jcm-10-02648-g001.jpg

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