Cancer is often imagined as a disease of uncontrolled growth, a mass of cells multiplying endlessly until they overwhelm the body. But the truth is both more complex and more haunting. Cancer cells are not only relentless in their desire to grow and divide—they are cunning. While most remain confined to their original tumor, others slip away like fugitives, traveling through the body in search of new places to call home.
This escape, known as metastasis, is one of cancer’s most dangerous tricks. It is especially insidious in breast cancer, where rogue cells can migrate to distant organs—the lungs, bones, liver, or brain—and remain silent for years. These cells don’t grow, don’t divide, don’t draw attention. They lie dormant, hidden like invisible landmines waiting for the right signal to explode into deadly new tumors.
For many breast cancer patients, the return of cancer years or even decades after initial treatment is one of the most devastating realities of the disease. Scientists have long wondered: What exactly jolts these sleeping cells awake?
A Scientist’s Long Pursuit
Robert Weinberg, a founding member of the Whitehead Institute and a pioneer in cancer biology at MIT, has devoted much of his career to answering this question. His work has transformed our understanding of how cancers spread and why they return. Together with his colleagues, including postdoctoral researcher Jingwei Zhang, Weinberg has now uncovered a surprising clue: dormant cancer cells may awaken not on their own, but because of signals from their surroundings.
In a recent study, their team revealed that inflammation in the tissues around dormant cancer cells acts like a wake-up call. Once stirred from their slumber, these cells don’t just grow again—they grow with new fury, forming aggressive tumors capable of invading and spreading further.
The Journey of Metastasis
To appreciate the significance of this discovery, it helps to understand the perilous path of metastasis. For a cancer cell to metastasize, it must break away from its original home. Most cells in our bodies are glued tightly to their neighbors by proteins on their surfaces—tiny molecular “velcro” that keeps tissues intact. But cancer cells, through genetic changes, can loosen this grip. Freed from the parent tumor, they become wanderers.
These wanderers slip into blood vessels or lymphatic channels, using the body’s circulatory systems as highways to distant organs. Yet, the journey is brutal. Most cancer cells perish along the way, destroyed by the immune system or crushed by sheer mechanical stress. Only a rare few endure, sneaking out of circulation and embedding themselves into new tissues far from their origin.
Even then, survival is far from guaranteed. The new environment is foreign, often hostile. Cancer cells arriving in the lungs or bones face a barrage of challenges—from immune defenses to a lack of compatible signals that normally guide cell behavior. To endure, many of them retreat into dormancy. They stop dividing, essentially pressing pause on their lives.
This dormant state is both a blessing and a curse. On one hand, it buys patients time, as dormant cells remain clinically undetectable. On the other, it makes them untouchable by most cancer treatments, which are designed to kill fast-dividing cells. The dormant seeds remain, waiting.
The Spark of Awakening
Weinberg and his colleagues wanted to know: what breaks this silence? What flips the switch that transforms dormant cancer cells into active, multiplying threats again?
Using mouse models, the team tracked human breast cancer cells that had migrated into the lungs. By tagging these cells with fluorescent proteins, the scientists could see whether they were dividing or lying dormant. In their studies, many cells indeed rested quietly in the lung tissue—until something changed.
The culprit, it turned out, was inflammation. When lung tissue became inflamed, dormant cancer cells stirred awake. The researchers demonstrated this effect using bleomycin, a chemotherapy drug that can cause scarring and inflammation in the lungs. When bleomycin induced lung inflammation, once-sleeping cancer cells suddenly began dividing, forming large, aggressive colonies.
This finding was chilling: a treatment meant to fight cancer could inadvertently help awaken dormant cancer cells in other tissues. But it also offered clarity about the forces at play.
The Role of the Tumor Microenvironment
What makes inflammation such a powerful signal? The answer lies in the tumor microenvironment—the ecosystem of immune cells, connective tissue, and signaling molecules that surround a tumor or a hidden cancer cell.
Weinberg’s team found that a particular type of immune cell, called M2 macrophages, played a starring role. These cells, which normally help with tissue repair, can release special molecules known as EGFR ligands. These ligands act like keys, unlocking receptors on the surface of dormant cancer cells. Once unlocked, a cascade of signals floods the cancer cell, jolting it out of dormancy and into rapid growth.
But the story doesn’t end there. Zhang and colleagues discovered something even more unsettling: once awakened, cancer cells carry what they call an “awakening memory.” Even after the inflammatory signals subside, the cells continue growing as though they cannot forget the wake-up call. The dormant state, once abandoned, is rarely returned to.
Why This Matters
The implications of this research are profound. Nearly 90% of cancer deaths come not from the original tumor but from metastasis. If scientists can better understand what awakens dormant cells, they may be able to prevent metastasis or at least delay it.
Imagine a future where oncologists could monitor dormant cancer cells and keep them silent indefinitely. Or where treatments could neutralize inflammatory signals before they reach cancer cells. Such strategies could transform cancer from a deadly threat into a chronic but manageable condition.
The Complexity of Cancer Signals
Of course, the biology is not simple. Inflammation is just one of many signals that can affect whether a dormant cell awakens. The body is a symphony of molecular communication, and cancer is a master at hijacking this music. Researchers know that multiple factors—from changes in blood vessels to shifts in immune activity—can all play a role.
Zhang emphasizes that understanding the full network of signals is essential. Cancer does not operate with a single trigger; it responds to a chorus. But identifying key players, such as EGFR signaling, gives scientists starting points for new therapies.
A Step Toward Hope
For patients living with breast cancer—or survivors who live with the fear of recurrence—these discoveries carry both sobering truths and rays of hope. The sobering truth is that cancer’s ability to hide and return is more sophisticated than once thought. But the hope is that every new piece of knowledge strengthens humanity’s ability to fight back.
Science advances not in leaps but in steps, each discovery adding a vital piece to the puzzle. The work of Weinberg, Zhang, and their colleagues is one such step, bringing us closer to therapies that could silence cancer’s landmines before they ever have a chance to explode.
The Larger Picture of Metastasis
At its heart, metastasis is a story of survival and adaptation. Cancer cells are not mindless—they are resourceful. They borrow the body’s own systems to travel, hide, and thrive. But science is resourceful too. By unmasking cancer’s strategies, researchers are turning its tricks against it.
The study of dormant cells is one of the most promising frontiers in cancer research today. If we can master the art of keeping these cells asleep—or erasing their “awakening memory”—we may tip the scales in favor of patients everywhere.
The Human Dimension
Behind every discovery lies not only science but also humanity. Each experiment is driven by the urgency of lives at stake. Every patient who faces recurrence, every family who fears the return of cancer, is part of the reason scientists pursue these questions with such intensity.
Cancer is not only a biological challenge but an emotional and human one. To understand metastasis is to fight not just for knowledge but for time—time for patients to live, to heal, to dream beyond their diagnosis.
Looking Forward
The journey toward curing cancer is far from over. But studies like this illuminate the path forward. They show us that cancer is not invincible; it is clever, but it can be understood. And what can be understood can eventually be outwitted.
By unraveling the secrets of dormancy and awakening, researchers are bringing us closer to a future where a diagnosis of breast cancer—or any cancer—no longer carries the same fear of recurrence. Instead, it will carry the promise of control, of treatment, and of life.
The silent awakening of dormant cancer cells may be one of the most dangerous aspects of cancer biology. But with each discovery, science grows louder, pushing back against the silence with knowledge, persistence, and hope.
More information: Jingwei Zhang et al, Inflammation awakens dormant cancer cells by modulating the epithelial–mesenchymal phenotypic state, Proceedings of the National Academy of Sciences (2025). DOI: 10.1073/pnas.2515009122
