How the National Cancer Institute is Unlocking Cancer's Physical Secrets
Imagine for a moment that cancer isn't just a biological disease, but a physical one—a condition where stiffness, pressure, and mechanical forces determine whether tumors spread or respond to treatment. This isn't science fiction; it's the cutting edge of cancer research happening today in labs funded by the National Cancer Institute (NCI).
While we've long focused on the genetic and molecular aspects of cancer, scientists are now revealing how the physical properties of tumors and their surroundings influence every aspect of the disease—from its initial development to its deadly spread throughout the body.
"The NCI has spearheaded this investigation into cancer's biomechanics, recognizing that understanding how physical forces shape tumor behavior could revolutionize how we detect, monitor, and treat this complex disease."
Healthy tissues have specific stiffness ranges that help maintain normal cell function. Cancer cells can dramatically alter this mechanical environment, creating stiffer tissues that promote tumor growth.
Cancer cells generate physical forces to migrate, invade new territories, and compress blood vessels. They can extend protrusions to pull themselves through tissue barriers 6 .
The flow of fluids within and around tumors influences how cancer cells spread through circulation. The mechanical stress from blood flow affects circulating tumor cells 1 .
The process of metastasis—where cancer cells spread to distant organs—demonstrates the profound importance of biomechanics. During this deadly cascade, cancer cells must physically deform to squeeze through tissue barriers, enter blood vessels, withstand fluid forces in circulation, and eventually force their way out to establish new tumors.
Research has revealed that cancer cells become softer and more deformable during metastasis, allowing them to survive the mechanical stresses of travel through the bloodstream 2 .
Stiffer cancer cells tend to establish bone metastases, while softer cells show preference for softer environments like the brain, demonstrating how mechanical matching influences where secondary tumors form 2 .
The National Cancer Institute has made strategic investments to advance cancer biomechanics research, recognizing its potential to transform our understanding and treatment of the disease.
Supports the development of advanced engineered models that mimic cancer pathophysiology, allowing researchers to study mechanical aspects of tumor growth and invasion 7 .
Supports research examining cancer through the lens of physical sciences, including mechanics, bringing new perspectives and methodologies to the field 1 .
Developing engineered biomimetic models of collective cancer invasion to screen chemotherapeutic agents 7 .
Creating vascularized microphysiological systems to model peritoneal carcinomatosis 7 .
Engineering the premetastatic niche to understand how tumors prepare new sites for colonization 7 .
Probing cellular, molecular and biomechanical barriers to immunotherapy using organotypic models 7 .
A recent prospective longitudinal study investigated whether mechanical properties of breast tumors can predict response to chemotherapy. Published in Breast Cancer Research in 2025, this study employed MR elastography to track changes in breast tumors during neoadjuvant chemotherapy (NAC) .
235 women with breast cancer undergoing NAC, with multifrequency MR elastography at four timepoints during treatment.
235 women with breast cancer scheduled for NAC .
Multifrequency MR elastography at four timepoints .
Shear-wave speed (stiffness) and loss angle (viscosity) .
Relationships between mechanical parameters and clinical outcomes .
The findings demonstrated that tumors with higher initial stiffness and viscosity were less likely to achieve complete response to chemotherapy. Mechanical parameters measured after just two cycles of treatment independently predicted which patients would eventually achieve pathologic complete response.
These results suggest that biomechanical properties provide clinically valuable information beyond what standard pathology reveals, potentially helping doctors identify earlier which patients may not respond to conventional chemotherapy .
Change in viscosity during early treatment phases was significantly associated with progression-free survival .
Measures mechanical properties of single cells and tissues. Used for quantifying stiffness changes in cancer cells versus normal cells 2 .
Non-invasive imaging of tissue mechanical properties. Used for tracking tumor stiffness changes during treatment .
Measures forces exerted by cells on their substrate. Used for studying how cancer cells pull themselves during migration 1 .
Sophisticated in vitro systems mimicking tumor microenvironment. Used for testing drug responses in relevant mechanical contexts 7 .
Replicates the mechanical environment of tumors. Allows more predictive drug testing outside the body 7 .
| Mechanical Property | Measurement Techniques | Cancer-Related Significance |
|---|---|---|
| Tissue Stiffness | MR elastography, Atomic Force Microscopy | Stiffer environments promote tumor progression and treatment resistance; predictive of chemotherapy response 2 |
| Cellular Elasticity | Atomic Force Microscopy, Optical Methods | Softer cancer cells are more deformable and metastatic; stiffness varies by cancer type and stage 2 |
| Interstitial Fluid Pressure | Micropipette insertion, Mathematical modeling | Elevated pressure in tumors impedes drug delivery and promotes metastasis 1 |
| Viscoelasticity | MR elastography, Rheometry | Tumor viscosity correlates with stroma content and predicts treatment outcomes |
| Cellular Traction Forces | Traction Force Microscopy, Micropost arrays | Forces generated by cancer cells enable migration through dense tissues 1 |
The ultimate goal of understanding cancer's biomechanics is to develop better ways to detect, treat, and prevent the disease. Several promising approaches are already emerging from this research:
Proteins such as PIEZO1 (a mechanosensitive ion channel), DDR1 (a collagen receptor), and YAP/TAZ (mechanosensitive transcription factors) represent promising new targets that operate through mechanical signaling 2 .
Researchers are designing innovative nanoparticle-based therapies specifically engineered to interfere with mechanical signaling pathways in cancer cells 6 .
The ability of MR elastography to predict chemotherapy response early in treatment suggests biomechanical imaging could soon help guide personalized treatment decisions .
The National Cancer Institute's strategic investment in biomechanics represents more than just support for another specialized research area—it signifies a fundamental expansion of how we conceptualize and confront cancer. By acknowledging that cancer is not merely a chemical and genetic disease but also a mechanical one, researchers are uncovering entirely new aspects of how tumors grow, spread, and resist treatment.
While the field is still developing, the progress to date suggests that understanding the physical forces within tumors will ultimately help us counter them more effectively. Through continued investment and investigation, the National Cancer Institute is ensuring that cancer's physical secrets won't remain hidden much longer—potentially opening new pathways to better treatments and improved outcomes for patients.