Physical traits of cancer
Physical traits of cancer
The biological and physical properties of tumors contribute to their growth and to treatment outcome. Although intense research efforts have helped to delineate cancer biology, the physics of cancer has only emerged in relatively recent times as a key area of research. Nia et al. reviewed the physical features that are common to tumors and that limit successful treatment: solid stresses, interstitial fluid pressure, stiffness (rigidity), and architecture and organization of tumor constituents. The authors provide a conceptual framework and discuss the origins of these distinct physical traits of cancer and how they enable and synergize with aberrant cancer biology to fuel cancer initiation, progression, immune evasion, and treatment resistance.
Historically, cancer has been considered a disease of the cell, caused by mutations in genes that control proliferation, differentiation, and death. In recent decades, however, the microenvironment surrounding the cancer cell has gained notoriety as a co-conspirator in tumor initiation, progression, immune evasion, and treatment response. As tumors grow, they disrupt the structure and function of the surrounding tissue via physical and biochemical mechanisms. The resulting physical abnormalities affect both cancer cells and their microenvironment and fuel tumorigenesis and treatment resistance. The links between cancer biology and physics have provided opportunities for the discovery of new drugs and treatment strategies.
Here, we propose four distinct physical cancer traits that capture the biomechanical abnormalities in tumors: (i) elevated solid stress, (ii) elevated interstitial fluid pressure, (iii) increased stiffness and altered material properties, and (iv) altered tissue microarchitecture. Solid stresses are created as proliferating and migrating cells push and stretch solid components of the surrounding tissue. Being distinct from fluid pressure and close to zero in most normal tissues, solid stresses are large enough to compress blood and lymphatic vessels in and around tumors, impairing blood flow and the delivery of oxygen, drugs, and immune cells. Acting at organ, tissue, and cellular levels, solid stresses activate signaling pathways that promote tumorigenesis and invasiveness and induce treatment resistance. Elevated interstitial fluid pressure is caused by leakage of plasma from abnormally permeable tumor blood vessels and insufficient lymphatic drainage. As a result, the interstitial fluid leaks out of the tumor into the peritumor tissue, causing edema and elution of drugs and growth factors and facilitating invasion and metastasis through flow-induced shear stresses. Increased stiffness is caused by matrix deposition and remodeling. Traditionally used as a diagnostic marker, and more recently as a prognostic factor, increased stiffness activates signaling pathways that promote proliferation, invasiveness, and metastasis of cancer cells. Finally, when normal tissue architecture is disrupted by cancer growth and invasion, microarchitecture is altered. Stromal and cancer cells and extracellular matrix adopt new organization. This changes the interactions between an individual cell and its surrounding matrix and cells, which affects signaling pathways associated with invasion and metastasis.
The tumor microenvironment is characterized by both biological and physical abnormalities. The growing appreciation of the role of tumor-stromal interactions in cancer has led to seminal discoveries that have resulted in previously unexplored targets and strategies for treatment. Understanding the key principles underlying the origins and consequences of the physical traits of cancer will be critical for improving treatment. Many of the concepts involved are nonintuitive and require deep and broad understanding of both the physical and biological aspects of cancer. Therefore, a rigorous but accessible description of physical cancer traits will assist research into the physical sciences of cancer—a highly multidisciplinary area—and help it remain an active and progressive subfield of cancer research.
To provide a comprehensive framework for understanding the links between the physics of cancer and signalling pathways in cancer biology in terms of a small number of underlying principles, we propose four physical traits of cancer that characterize the major physical abnormalities shared by most if not all tumors.
The role of the physical microenvironment in tumor development, progression, metastasis, and treatment is gaining appreciation. The emerging multidisciplinary field of the physical sciences of cancer is now embraced by engineers, physicists, cell biologists, developmental biologists, tumor biologists, and oncologists attempting to understand how physical parameters and processes affect cancer progression and treatment. Discoveries in this field are starting to be translated into new therapeutic strategies for cancer. In this Review, we propose four physical traits of tumors that contribute to tumor progression and treatment resistance: (i) elevated solid stresses (compression and tension), (ii) elevated interstitial fluid pressure, (iii) altered material properties (for example, increased tissue stiffness, which historically has been used to detect cancer by palpation), and (iv) altered physical microarchitecture. After defining these physical traits, we discuss their causes, consequences, and how they complement the biological hallmarks of cancer.