In a groundbreaking study published on July 30, 2025, in the prestigious journal Nature, researchers from the University of Colorado Anschutz Medical Campus, Montefiore Einstein Comprehensive Cancer Center (MECCC), and Utrecht University have unveiled direct evidence demonstrating that common respiratory viral infections, including SARS-CoV-2 (the virus responsible for COVID-19) and influenza, can reactivate dormant breast cancer cells that have metastasized to the lungs. This activation sets off the formation of new, aggressive metastatic tumors. The research, initially conducted using sophisticated mouse models, aligns closely with epidemiological data indicating heightened metastasis and mortality risks among cancer survivors who have contracted COVID-19.
The study addresses a critical gap in oncological research — understanding the triggers that cause disseminated cancer cells (DCCs), which remain quiescent after spreading from primary tumors, to awaken and proliferate, resulting in lethal metastatic disease. Dormancy of these cells often explains cancer relapse years after initial treatment, but the precise mechanisms underlying their reactivation have remained elusive. This multilayered investigation, combining molecular biology with population-level clinical data, elucidates a pivotal role for respiratory virus-induced inflammation in this process.
Key to these insights was the contribution of Dr. Julio Aguirre-Ghiso, co-leader of the study and director of the Cancer Dormancy Institute at MECCC. His lab’s unique mouse models mimic human metastatic breast cancer, particularly the dormancy of cancer cells within lung tissue. By infecting these animals with either SARS-CoV-2 or influenza virus, the researchers observed a rapid and robust awakening of dormant DCCs. Within days, these cells exited dormancy, proliferated extensively, and formed overt metastatic lesions within two weeks. This phenomenon was described metaphorically as dormant cancer cells being “embers” smoldering beneath the surface, with respiratory viruses acting as a “strong wind” rekindling the cancer’s latent fires.
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The molecular analysis uncovered the inflammatory cytokine interleukin-6 (IL-6) as a critical mediator in this viral-induced reawakening of dormant cancer cells. IL-6 is released by immune cells during infection and tissue injury and is known to play diverse roles in inflammation and immune regulation. In this context, the spike in IL-6 following respiratory viral infection acts as a biological switch, triggering signaling pathways within dormant DCCs that lead to their proliferation. This discovery holds significant therapeutic implications: targeting IL-6 signaling with established inhibitors may be an effective strategy to prevent or reduce metastatic relapses triggered by such viral infections.
Beyond the laboratory, the research team sought to corroborate their findings in human populations through extensive epidemiological studies. The first, leveraging the UK Biobank database, analyzed over 500,000 participants, focusing on cancer survivors who had been in remission for at least five years prior to the COVID-19 pandemic. Among these survivors, those who contracted COVID-19 demonstrated nearly double the risk of cancer-related mortality compared with matched controls who did not become infected. Crucially, deaths directly due to COVID-19 were excluded to isolate the increased risk arising from cancer progression itself. Notably, the risk of cancer mortality surged predominantly within the first year post-infection, mirroring the rapid metastatic expansion seen in animal models.
Complementing these findings, a second population study utilized the U.S.-based Flatiron Health database, encompassing data from 280 cancer clinics nationwide. Within a cohort of female breast cancer patients, those who contracted COVID-19 exhibited a 50% higher likelihood of developing lung metastases over an approximate 52-month follow-up period compared to those without COVID-19 infection. This substantial increase in metastatic progression emphasizes the real-world significance of viral infections as catalysts for cancer relapse and advances understanding of the long-term vulnerabilities faced by cancer survivors.
These converging lines of evidence underline the need for heightened vigilance and preventive measures within oncology practice. Patients with histories of cancer may benefit substantially from proactive vaccination strategies against common respiratory viruses and prompt clinical monitoring following respiratory infections. Dr. Aguirre-Ghiso stresses the importance of patient-provider communication to manage and mitigate these enhanced metastatic risks effectively.
The research team reinforces that their investigations are far from complete. There is strong intent to expand this line of inquiry to other cancer types and additional metastatic sites, recognizing that respiratory viral infections are an endemic presence in human populations worldwide. The findings call for ongoing efforts to delineate the fundamental biological mechanisms and identify therapeutic interventions that can protect cancer survivors from dormant cell reactivation triggered by viral insults.
One of the remarkable features of this study is its interdisciplinary nature, involving leading experts in oncology, immunology, molecular biology, and epidemiology from institutions across the United States and Europe. Senior author Dr. James DeGregori, deputy director of the CU Cancer Center, highlighted the collaborative effort describing it as “a village” of researchers uniting to tackle this complex biological puzzle. The integration of animal modeling with sophisticated immunological assays and large-scale human data sets exemplifies the power of multi-method approaches in addressing pressing medical challenges.
The article titled “Respiratory viral infections awaken metastatic breast cancer cells in lungs” emphasizes the link between inflammation induced by viral pathogens and cancer biology—a connection that had been suspected but not definitively proven until now. While prior studies had implied that severe inflammation could promote cancer progression, they lacked direct causal evidence, especially involving widely prevalent respiratory viruses. This study not only fills that void but also suggests actionable pathways for intervention and therapeutic development.
As respiratory virus variants continue to circulate globally, often causing seasonal outbreaks, the implications for cancer survivors are profound. This research compels a reevaluation of public health approaches, integrating viral prevention with oncological care to safeguard vulnerable populations. The identification of IL-6 signaling as a mechanistic nexus also opens new avenues for precision medicine, including the repurposing of IL-6 receptor antagonists or other immunomodulatory agents to shield dormant metastatic niches from awakening stimuli.
Ongoing research endeavors aim to refine understanding of the tumor microenvironment and immune interactions that orchestrate dormancy and reactivation dynamics. The Tumor Microenvironment and Metastasis Research Program at MECCC, led by Dr. Aguirre-Ghiso, continues to investigate the interplay between immune responses, extracellular matrix factors, and cytokine networks to develop robust mechanistic models. These insights could revolutionize metastasis prevention strategies, which are critical given that metastatic disease remains the primary cause of cancer mortality.
This study is a milestone in the evolving narrative of cancer biology, illustrating how seemingly unrelated events, such as viral respiratory infections, can exert outsized influence on cancer outcomes. It challenges researchers and clinicians alike to adopt a holistic perspective encompassing infectious diseases, immunology, and oncology to devise comprehensive patient management strategies in an era increasingly aware of the interconnections between different facets of human health.
In summary, this landmark research reveals that common respiratory infections can “awaken” dormant breast cancer cells residing in the lungs via IL-6 mediated inflammatory pathways, accelerating metastatic progression. The combination of rigorous animal experiments and large-scale human data analysis provides compelling evidence that cancer survivors face elevated risks after respiratory viral infections, highlighting the urgent need for integrated preventive and therapeutic approaches to address this emerging challenge in cancer care.
Subject of Research: The activation of dormant breast cancer cells by respiratory viral infections leading to metastatic progression.
Article Title: Respiratory viral infections awaken metastatic breast cancer cells in lungs.
News Publication Date: July 30, 2025.
Web References:
University of Colorado Anschutz Medical Campus: https://www.cuanschutz.edu/
Montefiore Einstein Comprehensive Cancer Center: https://montefioreeinstein.org/cancer
Utrecht University: https://www.uu.nl/en
Albert Einstein College of Medicine: https://einsteinmed.edu/
Nature DOI: http://dx.doi.org/10.1038/s41586-025-09332-0
References:
DeGregori J., Aguirre-Ghiso J., Rincon M., Vermeulen R., et al. (2025). Respiratory viral infections awaken metastatic breast cancer cells in lungs. Nature. DOI: 10.1038/s41586-025-09332-0.
Keywords: Cancer, Metastasis, Dormant Cancer Cells, Respiratory Viral Infections, COVID-19, Influenza, Interleukin-6, Inflammation, Breast Cancer, Tumor Dormancy, Metastatic Progression, Immunotherapy.
Tags: cancer dormancy and relapsecancer epidemiology and viral infectionsCOVID-19 and cancer survivorsinflammation and cancer progressioninfluenza and cancer metastasismetastatic breast cancer researchmolecular biology of cancer dormancyoncological implications of respiratory infectionsreactivation of dormant breast cancer cellsrespiratory viruses and cancer reactivationSARS-CoV-2 impact on cancerviral infections and tumor growth