Department of Molecular Cellular Biology, Osaka International Cancer Institute, Osaka, Japan.
Department of Biochemistry, Osaka International Cancer Institute, Osaka, Japan.
Cancer Sci. 2019 Feb;110(2):474-480. doi: 10.1111/cas.13917. Epub 2019 Jan 11.
The idea of tumor dormancy originated from clinical findings that recurrence of cancer occurs several years or even several decades after surgical resection of the primary tumor. Tumor mass dormancy was proposed as a model, where there is equal balance between increases in the number of cancer cells by proliferation and decreases as a result of cell death. Tumor mass dormancy includes angiogenic dormancy and immune-mediated dormancy. Another emerging type of tumor dormancy is cellular dormancy in which cancer cells are in a quiescent state. Cellular dormancy is induced by cues such as the extracellular matrix environment, metastatic niches, a hypoxic microenvironment, and endoplasmic reticulum stress. Even the oncogenic pathways, on which active cancer cells depend for survival and growth, are suppressed in the dormant state. As tumor dormancy is one of the mechanisms of resistance against various cancer therapies, targeting dormant cancer cells should be considered for future treatment strategies.
肿瘤休眠的概念源于临床发现,即原发性肿瘤切除后数年甚至数十年后癌症复发。肿瘤休眠被提出作为一种模型,其中癌细胞的增殖导致数量增加与细胞死亡导致数量减少之间存在平衡。肿瘤休眠包括血管生成休眠和免疫介导的休眠。另一种新兴的肿瘤休眠类型是细胞休眠,其中癌细胞处于静止状态。细胞休眠是由细胞外基质环境、转移龛位、缺氧微环境和内质网应激等信号诱导的。即使是癌细胞生存和生长所依赖的致癌途径,在休眠状态下也受到抑制。由于肿瘤休眠是抵抗各种癌症治疗的机制之一,针对休眠癌细胞应作为未来治疗策略的考虑因素。