The intersection of biology and physics is revealing startling insights about cancer and producing revolutionary treatments
For centuries, cancer has been viewed primarily through a biological lens—a disease of mutated genes and rogue cells. But what if we've been missing a crucial piece of the puzzle? Enter the physicists, armed with equations, force sensors, and a radically different perspective. They see tumors not just as biological entities, but as physical objects that obey the laws of mechanics, electricity, and fluid dynamics. This unlikely partnership between biology and physics is revealing startling insights about cancer and producing revolutionary treatments that might have seemed like science fiction just a decade ago.
Traditional view focusing on genetic mutations, cellular pathways, and molecular biology
Emerging view considering mechanical forces, electrical properties, and physical structures
The significance of this collaboration extends beyond academic curiosity. Despite extraordinary advances in cancer biology, mortality rates for many cancers still lag behind other diseases 1 . The physics of cancer offers fresh approaches to this stubborn problem. At research institutions worldwide, including the Physical Sciences-Oncology Network (PS-ON) established by the National Cancer Institute, physicists and biologists are working together to measure, model, and manipulate the physical properties of tumors 1 . Their findings are transforming our understanding of how cancer grows, spreads, and resists treatment—and more importantly, how we might stop it.
How mechanical properties of tissues drive malignant transformation
Tensile and compressive stresses that influence cancer behavior
Innovative treatments targeting cancer's physical vulnerabilities
For centuries, physicians have diagnosed cancer through palpation—feeling the characteristic stiffness of tumors. Today, we understand that this stiffness isn't just a symptom but an active participant in cancer progression. Tissue stiffness is now recognized as a physical property that can drive malignant transformation and tumor growth 1 .
The mechanical changes begin in the extracellular matrix (ECM), the scaffold that gives tissue its structure. Cancer-associated fibroblasts—cells recruited by the tumor—deposit excess proteins and promote collagen crosslinking, stiffening the matrix 2 . This stiff environment doesn't just provide physical support for tumors; it actively sends signals that encourage cancer cells to multiply and invade. Research has shown that increased stiffness can guide cell migration toward blood vessels, facilitating metastasis 2 .
Tumors exist in a world of physical forces that significantly influence their behavior:
Pulls tissues apart and appears to promote cell division. Experiments have shown that when this tension is released through collagen incisions, cancer invasion decreases 2 .
Can limit cancer cell proliferation by restricting volume expansion. These forces can compress blood vessels, limiting nutrient delivery and creating hypoxic conditions that may paradoxically drive metastasis in some cases 2 .
Use low-intensity, intermediate-frequency alternating electric fields to disrupt cell division. These fields appear to affect cancer cells during two critical phases of mitosis: disrupting mitotic spindle formation during metaphase, and interfering with separation of daughter cells during cytokinesis 3 .
Delivers radiation at ultrahigh dose rates—more than 1,000 times faster than conventional radiation. This approach maintains effectiveness against tumors while significantly reducing damage to normal tissues, a phenomenon known as the "FLASH effect" 4 . The precise mechanism is still being investigated, but it represents another promising application of physics to cancer treatment.
One of the most compelling examples of physics-based cancer therapy comes from research on Tumor Treating Fields. Let's examine a key experiment that demonstrated both the effectiveness and mechanism of this approach 3 .
Researchers selected multiple types of actively dividing cancer cells, placing them in standard laboratory conditions that encouraged growth and division.
The team applied TTFields using insulated electrodes generating low-intensity (2 V/cm) alternating electric fields at frequencies between 100-300 kHz. This specific range targets biological structures involved in cell division.
Scientists used advanced microscopy techniques to observe the effects of TTFields on cellular structures, particularly the mitotic spindle and chromosomes during cell division.
Through flow cytometry and other methods, researchers quantified how many cells were in each phase of the cell cycle, noting particular attention to accumulation in mitosis.
The team measured cell death rates using various markers, including caspase activation (indicating apoptosis) and the formation of multinucleated cells (suggesting failed divisions).
The TTFields experiment yielded several crucial findings:
Treated cells showed abnormal mitotic spindles—the structures that properly separate chromosomes during division. The ratio between polymerized and total tubulin (the building blocks of spindles) decreased significantly, indicating compromised spindle formation 3 .
Treated cells accumulated in the M phase (mitosis) of the cell cycle, suggesting they were stuck while attempting to divide. This prolonged mitosis often culminated in caspase-mediated apoptosis (programmed cell death) 3 .
Many treated cells developed abnormal chromosomal counts (aneuploidy) and became multinucleated—both indicators of severely disrupted cell division that typically leads to cell death 3 .
| Parameter Measured | Effect of TTFields | Biological Consequence |
|---|---|---|
| Mitotic spindle organization | Disrupted microtubule formation | Improper chromosome segregation |
| Cell cycle distribution | Accumulation in M phase | Prolonged mitosis leading to arrest |
| Chromosome count | Abnormal numbers (aneuploidy) | Genetic instability |
| Cellular structure | Multinucleated cells | Failed cell division |
| Cell viability | Increased caspase activation | Programmed cell death |
These findings demonstrated that TTFields successfully disrupt the physical processes of cell division, particularly targeting the mitotic spindle machinery and the final separation of daughter cells. The significance lies in the selective targeting of dividing cells—a hallmark of cancer—while largely sparing non-dividing healthy cells. This physical approach to disrupting cancer growth represents a fundamentally different strategy from traditional chemotherapy.
The intersection of biology and physics in cancer research has required—and inspired—the development of specialized tools and technologies. These approaches allow researchers to measure, model, and manipulate the physical properties of tumors and their environment.
| Tool/Technology | Function | Application in Cancer Research |
|---|---|---|
| Atomic force microscopy | Measures mechanical properties at nanoscale | Mapping stiffness of individual cancer cells and extracellular matrix |
| Tumor-on-a-chip devices | Microengineered culture models | Creating physiologically relevant 3D tumor models for studying cell dynamics 5 |
| Hi-C technology | Captures 3D chromatin organization | Studying how genome structure influences gene regulation in cancer 6 |
| In vivo microscopy | Real-time imaging in living organisms | Observing physical changes during invasion and metastasis 1 |
| TTFields devices | Deliver alternating electric fields | Disrupting cancer cell division for therapeutic purposes 3 |
| Scale of Analysis | Physical Properties | Biological Significance |
|---|---|---|
| Molecular | Protein flexibility, DNA mechanics | Influence on gene expression, response to damage |
| Cellular | Stiffness, deformability, traction forces | Ability to invade and metastasize 1 |
| Tissue | Elasticity, interstitial pressure, transport properties | Tumor growth, drug delivery efficiency 1 |
| Organ | Blood flow, mechanical stress | Effects on primary tumor and metastatic sites |
These tools enable researchers to bridge scales—from the nanomechanics of individual molecules to the bulk physical properties of entire tumors. The integration of computational modeling with experimental approaches has been particularly valuable, allowing scientists to simulate complex interactions that would be difficult to measure directly 1 .
The integration of physics into cancer biology represents more than just a new set of tools—it signifies a fundamental shift in how we understand and approach this complex disease. The physical properties of cancer cells and their environment are not merely secondary characteristics but active drivers of malignancy that interact dynamically with genetic and biochemical factors. This more comprehensive perspective is essential for developing innovative strategies to combat cancer.
Future cancer research will increasingly combine biological insights with physical principles to develop more effective treatments.
Continued development of physics-based tools will enable more precise measurement and manipulation of cancer's physical properties.
As this field advances, we can anticipate more sophisticated physics-based therapies that target the mechanical, electrical, and structural vulnerabilities of cancer. The ongoing development of technologies like FLASH radiotherapy, TTFields, and novel nanomedicine approaches suggests that the physical sciences will play an increasingly important role in oncology 3 4 . The future of cancer research lies not solely in understanding the biology of cancer, but in addressing it as a biophysical phenomenon—one that requires both biological and physical insights to fully comprehend and ultimately conquer.
The fight against cancer has often been described as a battle. Now, with physicists joining biologists in the trenches, we have new weapons, new strategies, and new hope for what might be possible.