The Increasing Role of the Tumor Microenvironment in Cancer Treatment Development
A new article by NFCR-supported scientist Dr. Valerie Weaver, titled “Tissue Mechanics in Tumor Heterogeneity and Aggression” (PMID: 40307158), was published in the April 2025 issue of Trends in Cancer. The article provides a comprehensive review of how the tumor microenvironment’s physical forces and mechanical properties regulate cancer progression, metastasis, immune evasion, and resistance to therapy. Dr. Weaver acknowledges support from the National Foundation of Cancer Research (NFCR) in this work.
Key Insights from Dr. Valerie Weaver’s article include:
- Mechanical Factors in Tumor Growth: The article emphasizes that increased tissue stiffness and remolding of the extracellular matrix (ECM)-the structural network surrounding cells- are key drivers of tumor initiation, progression, and aggregation. These physical changes activate cellular signaling pathways that support cancer cell survival, growth, invasion, and treatment resistance.
- Diversity in Tumor Behavior (Heterogeneity): The article explains that differences in the mechanical properties of the tumor microenvironment, such as ECM stiffness and tension, contribute to the development of diverse cancer cell types within the same tumor. This heterogeneity leads to variable levels of tumor aggressiveness and makes cancers more difficult to treat effectively.
- Implications for Treatment: Understanding how tissue mechanics influence tumor behavior could lead to innovative therapeutic approaches targeting tumors’ physical environment, such as reducing ECM stiffness or blocking mechanical signaling pathways. These strategies may improve drug delivery, overcome resistance, and enhance treatment effectiveness
What is the Tumor Microenvironment (TME)?
A Critical Therapeutic Frontier
The tumor microenvironment encompasses the complex cellular ecosystem surrounding a tumor, which is critical in supporting or restraining cancer progression. It comprises cancer cells, stromal cells, immune cells, blood vessels, and the surrounding ECM. Dr. Weaver’s research illustrates how the mechanical features of this ecosystem shape cancer cell behavior and therapeutic outcomes. Her work builds on foundational advances by other NFCR-supported scientists like Dr. Rakesh K. Jain, who was recognized with the 2022 Szent-Györgyi Prize for Progress in Cancer Research for work on overcoming the physical barriers of the TME to improve drug delivery.
Understanding tumor-microenvironment interactions has emerged as a therapeutic frontier for developing more effective cancer treatments. Learn more about this Focus Area of Research >>>
Collaborative Research Spotlight: Glycosylation and Metastasis
Currently, Dr. Weaver is collaborating with Dr. Kornelia Polyak, also supported by NFCR, to investigate how differences in sugar molecules attached to cancer cells in primary breast tumors compare to those attached to brain metastatic cancer cells, and how these differences affect the cancer cell’s response to treatment.
Looking Ahead: Personalized, Mechanically-Informed Therapies
Dr. Weaver’s article concludes that future cancer treatments should consider genomic and molecular profiles as well as the tumor’s physical and mechanical landscape. Personalized therapies that integrate biomechanical assessments with targeted treatments could lead to better outcomes, particularly for patients with aggressive or therapy-resistant cancers.
About Dr. Valerie Weaver
Dr. Valerie Weaver is a leading expert in tumor mechanobiology and is supported by NFCR to explore how mechanical forces in the tumor microenvironment affect cancer development and response to treatment. Her interdisciplinary research spans breast, pancreatic, and brain cancers, with a focus on uncovering new therapeutic targets tied to tissue mechanics and ECM biology.
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The transformative research led by Dr. Weaver and other NFCR-supported scientists is made possible by the generosity of our donors. Your contributions help fund pioneering cancer research and accelerate the discovery of innovative therapies that offer hope to patients worldwide.
