Paul Papin ICO Cancer Center, CRCINA, INSERM, Université de Nantes, Université d'Angers , Angers , France.
SIRIC ILIAD , Nantes, Angers , France.
Cell Cycle. 2019 Oct;18(19):2385-2397. doi: 10.1080/15384101.2019.1652047. Epub 2019 Aug 9.
Senescence is activated in response to chemotherapy to prevent the propagation of cancer cells. In transformed cells, recent studies have shown that this response is not always definitive and that persistent populations can use senescence as an adaptive pathway to restart proliferation and become more aggressive. Here we discuss the results showing that an incomplete and heterogeneous senescence response plays a key role in chemotherapy resistance. Surviving to successive chemotherapy regimens, chronically existing senescent cells can create a survival niche through paracrine cooperations with neighboring cells. This favors chemotherapy escape of premalignant clones but might also allow the survival of adjacent clones presenting a lower fitness. A better characterization of senescence heterogeneity in transformed cells is therefore necessary. This will help us to understand this incomplete response to therapy and how it could generate clones with increased tumor capacity leading to disease relapse.
衰老会被化疗激活，以防止癌细胞的增殖。在转化细胞中，最近的研究表明，这种反应并不总是确定的，持续存在的细胞群可以将衰老作为一种适应性途径来重新启动增殖并变得更具侵略性。在这里，我们讨论了表明不完全和异质衰老反应在化疗耐药性中起关键作用的结果。幸存下来的连续化疗方案，慢性存在的衰老细胞可以通过与邻近细胞的旁分泌合作创造一个生存小生境。这有利于恶性前克隆逃避化疗，但也可能允许生存相邻的克隆具有较低的适应性。因此，有必要更好地描述转化细胞中的衰老异质性。这将帮助我们理解这种对治疗的不完全反应，以及它如何产生具有增加肿瘤能力的克隆，导致疾病复发。
