癌症在化疗后再发的主要原因是癌细胞从休眠中逃脱。紫杉醇类化疗是针对乳腺癌的标准治疗方法，旨在杀死增殖的癌细胞。在这里，我们证明多西他赛会损害基质细胞，并释放促肿瘤细胞因子IL-6和粒细胞集落刺激因子（G-CSF），从而在体外和体内调用休眠癌细胞的生长。单细胞转录组学展示了唤醒的癌细胞的重新编程，包括干细胞特性、对化疗的耐药性等多个生存信号，在肿瘤基质类器官（TSO）模型及同种基因小鼠乳腺癌模型中，肿瘤微环境（TME）的改变及增强的促肿瘤免疫信号。IL-6在癌细胞增殖中发挥作用，而G-CSF介导肿瘤免疫抑制。通路和差异表达分析证实了MEK是调节癌细胞生长和存活的关键分子。通过靶向促肿瘤细胞因子（IL-6、G-CSF）的抗体或使用selumetinib抑制MEK/ERK通路的细胞因子信号，在多西他赛治疗前可以预防癌细胞的休眠生长，这提供了一个预防癌症复发的新治疗策略。 版权所有：© 2023 Ganesan等人。本文为开放获取文章，依照知识共享许可协议，允许在任何媒体中自由使用、分发和复制，只要原作者和来源被归功于。

A major cause of cancer recurrence following chemotherapy is cancer dormancy escape. Taxane-based chemotherapy is standard of care in breast cancer treatment aimed at killing proliferating cancer cells. Here, we demonstrate that docetaxel injures stromal cells, which release protumor cytokines, IL-6 and granulocyte colony stimulating factor (G-CSF), that in turn invoke dormant cancer outgrowth both in vitro and in vivo. Single-cell transcriptomics shows a reprogramming of awakened cancer cells including several survival cues such as stemness, chemoresistance in a tumor stromal organoid (TSO) model, as well as an altered tumor microenvironment (TME) with augmented protumor immune signaling in a syngeneic mouse breast cancer model. IL-6 plays a role in cancer cell proliferation, whereas G-CSF mediates tumor immunosuppression. Pathways and differential expression analyses confirmed MEK as the key regulatory molecule in cancer cell outgrowth and survival. Antibody targeting of protumor cytokines (IL-6, G-CSF) or inhibition of cytokine signaling via MEK/ERK pathway using selumetinib prior to docetaxel treatment prevented cancer dormancy outgrowth suggesting a novel therapeutic strategy to prevent cancer recurrence.Copyright: © 2023 Ganesan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.