The role of mechanical forces in tumor growth and therapy

Annu Rev Biomed Eng. 2014 Jul 11;16:321-46. doi: 10.1146/annurev-bioeng-071813-105259.

Abstract

Tumors generate physical forces during growth and progression. These physical forces are able to compress blood and lymphatic vessels, reducing perfusion rates and creating hypoxia. When exerted directly on cancer cells, they can increase cells' invasive and metastatic potential. Tumor vessels-while nourishing the tumor-are usually leaky and tortuous, which further decreases perfusion. Hypoperfusion and hypoxia contribute to immune evasion, promote malignant progression and metastasis, and reduce the efficacy of a number of therapies, including radiation. In parallel, vessel leakiness together with vessel compression causes a uniformly elevated interstitial fluid pressure that hinders delivery of blood-borne therapeutic agents, lowering the efficacy of chemo- and nanotherapies. In addition, shear stresses exerted by flowing blood and interstitial fluid modulate the behavior of cancer and a variety of host cells. Taming these physical forces can improve therapeutic outcomes in many cancers.

Keywords: solid stress; stress alleviation; tumor microenvironment; tumor perfusion; vascular hyperpermeability; vascular normalization; vessel compression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Disease Progression
  • Drug Delivery Systems
  • Extracellular Fluid
  • Humans
  • Hypoxia
  • Immune System
  • Lymph
  • Microcirculation
  • Models, Theoretical
  • Neoplasm Metastasis
  • Neoplasms / pathology
  • Neoplasms / physiopathology*
  • Neoplasms / therapy*
  • Perfusion
  • Shear Strength
  • Stress, Mechanical
  • Vascular Endothelial Growth Factor A / chemistry

Substances

  • Vascular Endothelial Growth Factor A