我们对转移过程了解多少?

IF 4.2 3区 医学 Q2 ONCOLOGY
Clinical & Experimental Metastasis Pub Date : 2024-08-01 Epub Date: 2024-03-23 DOI:10.1007/s10585-023-10248-0
Carolina Rodriguez-Tirado, Maria Soledad Sosa
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引用次数: 0

摘要

即使在肿瘤进展的早期和无症状阶段,癌细胞也能离开原发部位,通过血液循环到达远处,在那里以播散癌细胞(DCC)的形式存活。在实验模型和临床样本中,可以检测到处于非增殖状态的 DCCs,这种状态被定义为细胞休眠。这种状态可持续很长时间,直到 DCCs 重新唤醒,通常是对龛源性重新激活信号做出反应。因此,临床上在淋巴结和骨髓等部位发现 DCC 与生存率低下有关。目前的癌症疗法设计基于原发肿瘤的生物学特性,并不针对休眠 DCC 群体的生物学特性,因此无法根除最初或随后的转移浪潮。在这篇简短的综述中,我们讨论了目前检测 DCC 的方法,并重点介绍了旨在针对构成最小残留病灶的 DCC 以减少或防止转移形成的新策略。此外,我们还介绍了从肿瘤进展早期阶段提取的 DCCs 与转移性疾病相关性的现有证据,并描述了可用于研究 DCCs 的动物模型。我们还讨论了目前对基因较低和较先进的癌细胞所利用的扩散机制的理解,其中包括对上皮-间质转化(EMT)的中间状态或混合状态的功能分析。最后,我们提出了一些耐人寻味的问题,这些问题涉及研究 DCCs 演化浪潮与转移性疾病发生之间的相互关系对临床的影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

How much do we know about the metastatic process?

How much do we know about the metastatic process?

Cancer cells can leave their primary sites and travel through the circulation to distant sites, where they lodge as disseminated cancer cells (DCCs), even during the early and asymptomatic stages of tumor progression. In experimental models and clinical samples, DCCs can be detected in a non-proliferative state, defined as cellular dormancy. This state can persist for extended periods until DCCs reawaken, usually in response to niche-derived reactivation signals. Therefore, their clinical detection in sites like lymph nodes and bone marrow is linked to poor survival. Current cancer therapy designs are based on the biology of the primary tumor and do not target the biology of the dormant DCC population and thus fail to eradicate the initial or subsequent waves of metastasis. In this brief review, we discuss the current methods for detecting DCCs and highlight new strategies that aim to target DCCs that constitute minimal residual disease to reduce or prevent metastasis formation. Furthermore, we present current evidence on the relevance of DCCs derived from early stages of tumor progression in metastatic disease and describe the animal models available for their study. We also discuss our current understanding of the dissemination mechanisms utilized by genetically less- and more-advanced cancer cells, which include the functional analysis of intermediate or hybrid states of epithelial-mesenchymal transition (EMT). Finally, we raise some intriguing questions regarding the clinical impact of studying the crosstalk between evolutionary waves of DCCs and the initiation of metastatic disease.

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来源期刊
CiteScore
7.80
自引率
5.00%
发文量
55
审稿时长
12 months
期刊介绍: The Journal''s scope encompasses all aspects of metastasis research, whether laboratory-based, experimental or clinical and therapeutic. It covers such areas as molecular biology, pharmacology, tumor biology, and clinical cancer treatment (with all its subdivisions of surgery, chemotherapy and radio-therapy as well as pathology and epidemiology) insofar as these disciplines are concerned with the Journal''s core subject of metastasis formation, prevention and treatment.
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