Findings from a Chinese study showed that chemotherapy, while essential in shrinking tumors, may paradoxically accelerate cancer spread by awakening dormant cells. Researchers discovered that certain drugs, particularly doxorubicin and cisplatin, stimulate processes that allow breast cancer cells to reemerge from dormancy and form metastases in the lungs.
How Chemotherapy Awakens Dormant Cancer Cells
The study was made possible through the development of the DormTracer genetic tracing tool. This advanced system allowed scientists to label dormant disseminated tumor cells and monitor their behavior. It also enabled researchers Dasa He et al. to observe how chemotherapy influenced the reactivation of these cells and the mechanism behind cancer recurrence.
Findings indicated that chemotherapy does not directly stimulate dormant cancer cells. Instead, it damages surrounding fibroblasts within the lungs, forcing them into a state of senescence. These aging fibroblasts then create conditions that encourage immune cells to release neutrophil extracellular traps, a process that remodels the tissue environment.
Note that fibroblasts are connective tissue cells responsible for producing and maintaining the extracellular matrix, particularly collagen and other structural proteins. They play essential roles in wound healing, tissue repair, and structural support. In the lungs, they are crucial for maintaining structural integrity and supporting normal respiratory function.
The remodeling of lung tissue due to chemotherapy ultimately awakens previously silent cancer cells and prompts them to grow again. This explains why some breast cancer patients experience metastasis after what seems to be successful treatment of the original tumor. The discovery shows complex interactions between therapy, host response, and tumor biology.
Proposed Approaches to Prevent Cancer Recurrence
Researchers tested potential countermeasures. One approach involved combining chemotherapy with senolytic drugs. These included a regimen of dasatinib and quercetin. In laboratory models, this combination successfully eliminated senescent cells, thus reducing the chance of dormant cancer cells reawakening and spreading within the lungs.
Another intervention targeted the neutrophil extracellular traps directly. Treatments that disrupted the formation of these traps, such as DNase I or PAD4 inhibitors, also reduced chemotherapy-induced metastasis in animal experiments. These strategies show potential for protecting patients against relapse while preserving the primary benefits of chemotherapy.
Clinical relevance was established via analysis of breast cancer patients. Their lung metastases displayed higher neutrophil trap density and increased inflammatory signals like C3, MIF, and CXCL1. These molecular markers may serve as predictors for relapse risk and provide doctors with potential indicators to anticipate and manage disease progression.
Another study also found that respiratory viral infections could awaken dormant breast cancers lodged in the lungs. Researchers S. B. Chia et al. noted that breast cancer patients who have achieved years of remission may still need to exercise caution regarding respiratory infections. The role of the immune response to the infection was linked to cancer resurgence.
FURTHER READINGS AND REFERENCES
- He, D., Wu, Q., Tian, P., Liu, Y., Jia, Z., Li, Z., Wang, Y., Jin, Y., Luo, W., Li, L., Zhang, P., Jin, Q., Zhao, W., Hu, W., Liang, Y., Zhou, B., Yang, Q., Jiang, Y., Shao, Z.-M., and Hu, G. 2025. “Chemotherapy Awakens Dormant Cancer Cells in the Lung by Inducing Neutrophil Extracellular Traps.” Cancer Cell. DOI: 1016/j.ccell.2025.06.007
- Chia, S. B., Johnson, B. J., Hu, J., Valença-Pereira, F., Chadeau-Hyam, M., Guntoro, F., Montgomery, H., Boorgula, M. P., Sreekanth, V., Goodspeed, A., Davenport, B., De Dominici, M., Zaberezhnyy, V., Schleicher, W. E., Gao, D., Cadar, A. N., Petriz-Otaño, L., Papanicolaou, M., Beheshti, A., … DeGregori, J. 2025. “Respiratory Viral Infections Awaken Metastatic Breast Cancer Cells in Lungs.” Nature. DOI: 1038/s41586-025-09332-0