New Research: How Systemic Inflammation Can Reactivate Dormant Cancer Cells

For decades, oncologists have known that cancer can come back years or even decades after a patient was thought to be cured. In breast cancer, late recurrences appearing ten or twenty years after initial treatment are not rare, and they represent one of the most unsettling features of the disease. The leading explanation for this phenomenon is cancer dormancy: the idea that small numbers of tumor cells leave the primary site early, travel through the bloodstream, and take up residence in distant organs, particularly in the bone marrow, where they enter a quiet, non-dividing state. They are not growing, so they are not detectable. But they are not gone either. Something, at some point, wakes them up.

Identifying what breaks that dormant state has been one of oncology's harder problems. Physical disruption such as a fracture near a bone metastasis has long been known to trigger reactivation. But the new research from Ilaria Malanchi's laboratory at the Francis Crick Institute points toward a more systemic trigger: inflammation happening elsewhere in the body, as far away from the bone as the gut.

What the Francis Crick Institute Study Did

The research team built an engineered model of bone that could be implanted in mice and would behave like real bone marrow. These extramedullary (outside the natural bone) constructs were grown from skeletal stem cells and integrated with the mouse's own vasculature, meaning they responded to the animal's immune system just as natural bones do. When the researchers introduced breast cancer cells into the model bone, most of the tumor cells entered dormancy, showing only occasional and transient bursts of replication. The model essentially reproduced in a controllable setting the kind of dormancy seen in clinical patients.

The key experiment involved inducing gut inflammation in the mice carrying dormant cancer cells in their artificial bone. The researchers triggered intestinal colitis, a form of inflammation that does not directly touch the bone but creates a systemic inflammatory state that circulates through the bloodstream. Within the engineered bone, this gut inflammation triggered a rapid increase in the production of immune cells, a process called emergency granulopoiesis, in which the bone marrow ramps up its output of white blood cells in response to a perceived systemic threat.

It was the immune cell surge, not the gut inflammation itself, that disturbed the dormant cancer cells. Genetic analysis of the tissue revealed that the growth-stimulating molecule HMGB2 (High-Mobility Group Box 2) rose in parallel with the increased immune cell production. When the team introduced HMGB2 directly into the artificial bone without any outside inflammation, that was enough on its own to activate sleeping cancer cells and increase the rate at which they developed into overt metastases. The molecule appeared to be the key intermediary: systemic inflammation raised it, and raised HMGB2 broke dormancy.

The study was published in Cell Reports on October 1, 2026 (Di Blasio et al., 2026).

The Human Evidence

Moving from mice to humans is always the critical step, and the Crick team found a meaningful signal in human tissue. The researchers examined bone samples from breast and prostate cancer patients and looked for HMGB2. They found it present specifically at sites where active cell division was occurring, the places where dormant cells appeared to have re-entered the cell cycle. This does not prove that HMGB2 caused the reactivation in those patients, since the samples are observational rather than experimental, but it establishes that the protein is present in the right context in human cancer biology. The correlation is consistent with the mechanism the mouse model revealed.

The research also found that the effect extended beyond the artificial bone to the mice's natural bones. When the animals with dormant cancer in their engineered bone tissue experienced the gut inflammation, the incidence of cancer spreading to their real bone also increased. This suggests the mechanism operates in natural tissue, not just in the experimental construct, and that systemic inflammatory states may genuinely alter the conditions inside real bone marrow.

Why HMGB2 Matters

HMGB2 is a nuclear protein that normally helps regulate gene expression inside cells, but it can also act outside cells as a signaling molecule. It belongs to the same family as HMGB1, which is already well known in inflammation research as a damage-associated molecular pattern (DAMP), a signal the body releases to indicate tissue damage or stress. HMGB proteins are often released when cells are injured, dying, or under severe stress, and they communicate the state of danger to surrounding tissue. The Crick study suggests that HMGB2, while less studied than its sibling, plays a specific role in instructing bone marrow cells about the body's inflammatory status, and that this signal inadvertently tells dormant cancer cells to start growing.

What is striking about the mechanism is how indirect it is. The inflammation does not need to be in the bone itself. Gut inflammation, the kind that can arise from infection, inflammatory bowel conditions, or other stressors, was enough to send a systemic signal through the bone marrow that altered the fate of cells sitting in a completely different part of the body. This points toward the whole-body nature of the inflammatory state as something that matters for cancer biology, not just for the local tissue where inflammation is most visible.

This Finding Fits a Broader Pattern

The idea that inflammation can break cancer dormancy has been building in the research literature for several years. A separate line of research has focused on neutrophil extracellular traps (NETs), web-like structures that neutrophils release during inflammatory responses. A 2025 study in Cancer Cell found that chemotherapy-induced inflammation caused fibroblasts to senesce and release factors that stimulated NETs from neutrophils, and those NETs then reactivated dormant cancer cells in the lung by remodeling the extracellular matrix around them (He et al., 2025). The study found that combining senolytic drugs with chemotherapy could suppress this post-therapy dormancy awakening, which opens a potential therapeutic direction.

The Crick study adds a different mechanism to this picture. Rather than NETs and matrix remodeling, it identifies emergency granulopoiesis and HMGB2 as a distinct pathway by which systemic inflammation disrupts dormancy. The two studies together suggest that there is not one single way inflammation wakes up sleeping cancer cells but rather several converging pathways, all triggered by the body's broad inflammatory response to perceived threats.

The connection between cancer biology and bone marrow is also well established in the literature on dormancy. Reviews of prostate and breast cancer dormancy consistently identify the bone marrow as one of the most important reservoirs for disseminated tumor cells, noting that these cells can persist in a quiescent G0 state for extended periods controlled by signals from the local microenvironment (Cackowski and Heath, 2021). The Crick study advances this field by demonstrating for the first time, in a controlled experimental system, that inflammation originating outside the bone can penetrate that microenvironment and shift the balance toward reactivation.

What Drives Emergency Granulopoiesis in Real Life

Emergency granulopoiesis, the bone marrow response that the Crick study found was driving HMGB2 and dormancy disruption, is not an exotic event. It is the bone marrow's standard response to systemic infection, injury, or severe inflammation. When the body detects a major immune challenge, whether from a bacterial infection, a serious viral illness, a gut flare, or other sources of sustained inflammatory stress, the bone marrow accelerates white blood cell production to meet the demand. Under ordinary circumstances, this is a life-saving response. The new research suggests it may come with a cost for people who have dormant cancer cells residing in their bone marrow.

This raises obvious questions about chronic low-grade inflammation, the kind that does not come from a single acute infection but from sustained lifestyle-driven factors. Chronic inflammation from excess body fat, a diet high in ultra-processed foods, persistent psychological stress, poor sleep, or long-term smoking keeps inflammatory signaling elevated at a lower level than acute infection but over much longer timescales. Whether that chronic background level produces meaningful emergency granulopoiesis signals is something the current research does not directly address. The Crick study used an acute colitis model, not a model of chronic low-grade inflammation. But the finding adds biological plausibility to the general principle that keeping systemic inflammation in check is meaningful for people with a cancer history, beyond the cardiovascular and metabolic reasons that already motivate inflammation management.

The researchers themselves noted that this finding points toward a potential vulnerability in the recovery phase after cancer treatment. Surgery, chemotherapy, and radiation all trigger significant inflammatory responses in the body. If those treatment-related inflammatory signals temporarily raise HMGB2 in the bone marrow, they could, in theory, disturb dormant cancer cells at exactly the time when the patient appears to be responding to treatment. This is speculative, but it is a hypothesis the field will likely investigate in coming years, particularly in light of the parallel findings in the NETs literature.

Limitations and What the Research Does Not Say

This is preclinical research, and preclinical findings often do not translate directly to clinical practice. The study used engineered bone tissue and mouse models of gut inflammation, not human patients in clinical trials. The finding that HMGB2 is present in human bone samples at sites of cell division is observational evidence, not proof of causation. The mechanisms governing cancer dormancy in humans are likely more complex than what any single model captures, and the conditions under which dormancy breaks in actual patients may involve many interacting factors beyond HMGB2 alone.

Importantly, this research does not mean that managing inflammation will prevent cancer recurrence. No study has yet shown that reducing systemic CRP levels or other inflammatory markers in cancer survivors reduces their risk of late relapse. That is a clinical hypothesis worth testing, but it has not been tested in a rigorous randomized trial. The research is best understood as establishing a mechanism, not as a guide to clinical decision-making. Any decisions about monitoring or managing inflammation in the context of a personal cancer history belong in a conversation with an oncologist.

Inflammation as a Systemic Signal Worth Tracking

What the Crick study contributes, beyond its specific mechanistic finding, is evidence that inflammation is not just a local event. The same systemic inflammatory state that raises CRP in the blood, drives atherosclerosis in the arteries, and disrupts sleep quality is apparently also capable of sending signals into the bone marrow that alter the behavior of cells residing there. Inflammation is a whole-body phenomenon, and its effects reach places that are not obviously inflamed.

C-reactive protein, the marker Sensa measures, is one of the most accessible windows into systemic inflammatory status. CRP is produced by the liver in response to cytokines including IL-6 and TNF-alpha, exactly the kinds of signals that drive the sort of systemic immune activation the Crick study examined. Tracking CRP over time does not tell you whether you have dormant cancer cells, and it is not intended for that purpose. But it does reflect the inflammatory state of the whole body, and the research landscape is increasingly clear that that state matters for a wide range of biological processes, including some that bear on long-term health outcomes in ways researchers are only beginning to understand.

Sensa is a general wellness product designed to help people track their inflammatory trends at home as part of a broader approach to healthy living. If you have concerns about your health or a personal history of cancer, those conversations belong with qualified healthcare providers.

Sources

• Di Blasio S, Rizou T, Gay LJ, et al. An extramedullary bone model of metastatic dormancy reveals an increased rate of metastatic reactivation upon distant insults. Cell Reports, 2026. pubmed.ncbi.nlm.nih.gov/42822459
• He D, Wu Q, Tian P, et al. Chemotherapy awakens dormant cancer cells in lung by inducing neutrophil extracellular traps. Cancer Cell, 2025. pubmed.ncbi.nlm.nih.gov/40614736
• Cackowski FC, Heath EI. Prostate cancer dormancy and recurrence. Cancer Letters, 2021. pubmed.ncbi.nlm.nih.gov/34624433
• MedicalXpress. Inflammation can reactivate 'sleeping' cancer cells hidden in the bone. October 2, 2026. medicalxpress.com

Frequently Asked Questions

Can chronic inflammation cause cancer to come back?

Research suggests that systemic inflammation can disrupt the biological conditions that keep dormant cancer cells inactive. A 2026 study published in Cell Reports found that gut inflammation in animal models raised levels of a protein called HMGB2, which reactivated dormant breast cancer cells in bone marrow. While this research does not prove that managing your inflammation will prevent cancer recurrence, it adds to a growing body of evidence that chronic inflammatory signaling is a factor the field considers seriously. Any concerns about cancer recurrence should be discussed with an oncologist.

What is HMGB2 and why does it matter for cancer?

HMGB2 (High-Mobility Group Box 2) is a nuclear protein that plays a role in regulating gene expression. The 2026 Francis Crick Institute research identified it as the key molecule linking systemic inflammation to the reactivation of dormant cancer cells in bone. When inflammation triggered emergency immune cell production in their animal model, HMGB2 levels rose, and simply introducing HMGB2 into the engineered bone tissue without any outside inflammation was enough to activate sleeping cancer cells. HMGB2 was also found in human bone samples from breast and prostate cancer patients at sites of active cell division.

What is cancer dormancy and how long can it last?

Cancer dormancy refers to a state in which disseminated tumor cells travel to a distant organ, such as the bone marrow, but remain quiescent and do not grow into detectable tumors. These cells can persist in this inactive state for years or even decades after a patient appears cured. The bone marrow is considered one of the most important sites for dormant tumor cells, particularly in breast and prostate cancer. Dormancy can end through changes in the local tissue environment or, as new research suggests, through systemic signals such as inflammation.

Should people who have had cancer monitor their inflammation levels?

Tracking CRP or other inflammation markers after a cancer diagnosis is a topic to discuss with your oncologist, as medical management of inflammation in cancer survivors is a specialized clinical question. Sensa is a general wellness product designed for lifestyle monitoring, not for cancer management or disease monitoring. If you have a personal cancer history and are interested in tracking your overall inflammatory state as part of a healthy lifestyle, talk with your healthcare team first about what makes sense for your situation.