中国科学院上海营养与健康研究所胡国宏团队取得一项新突破。他们揭示了化疗通过诱导中性粒细胞胞外陷阱唤醒休眠的肺癌细胞。相关论文发表在2025年7月3日出版的《癌细胞》杂志上。

课题组证明化疗药物，包括阿霉素和顺铂，促进休眠乳腺癌细胞的增殖和肺转移。使用基于重组酶的休眠追踪系统DormTracer，该研究团队证实了化疗诱导的休眠dtc的再激活导致转移性复发。从机制上讲，化疗诱导成纤维细胞衰老，通过分泌蛋白质促进中性粒细胞胞外陷阱（NETs）的形成。NETs通过细胞外基质重塑促进休眠DTC增殖。重要的是，抗衰老药物达沙替尼和槲皮素与阿霉素联合使用可抑制治疗后DTC的再激活并抑制转移性复发。该研究提供了休眠唤醒的直接证据，揭示了化疗对转移有害影响的机制，突出了改善癌症治疗的潜在策略。

据悉，播散性肿瘤细胞（DTCs）可以在远处器官中保持非增殖性休眠状态数年，但引发其再激活和转移定植的外源性抗原尚不清楚。

附：英文原文

Title: Chemotherapy awakens dormant cancer cells in lung by inducing neutrophil extracellular traps

Author: Dasa He, Qiuyao Wu, Pu Tian, Yin Liu, Zhenchang Jia, Zhenwei Li, Yuan Wang, Yuchen Jin, Wenqian Luo, Ling Li, Peiyuan Zhang, Qianlu Jin, Wenjing Zhao, Weiguo Hu, Yajun Liang, Bin Zhou, Qifeng Yang, Yi-zhou Jiang, Zhi-Ming Shao, Guohong Hu

Issue&Volume: 2025-07-03

Abstract: Disseminated tumor cells (DTCs) can remain in a non-proliferative, dormant state for years in distant organs, but the exogenous causes triggering their reactivation and metastatic colonization are unclear. Here, we demonstrate that chemotherapeutic drugs, including doxorubicin and cisplatin, enhance proliferation and lung metastasis of dormant breast cancer cells. Using a recombinase-based dormancy tracing system, DormTracer, we confirm chemotherapy-induced reactivation of dormant DTCs leading to metastatic relapse. Mechanistically, chemotherapy induces fibroblast senescence, which promotes formation of neutrophil extracellular traps (NETs) through secreted proteins. NETs promote dormant DTC proliferation through extracellular matrix remodeling. Importantly, combining senolytic drugs, dasatinib and quercetin, with doxorubicin inhibits post-therapy DTC reactivation and suppresses metastatic relapse. This study provides direct evidence of dormancy awakening and reveals a mechanism underlying detrimental effect of chemotherapy on metastasis, highlighting potential strategies to improve cancer treatment.

DOI: 10.1016/j.ccell.2025.06.007

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00257-0