A Poroelasticity Theory Approach to Study the Mechanisms Leading to Elevated Interstitial Fluid Pressure in Solid Tumours

Andrijana Burazin, Corina S. Drapaca, Giuseppe Tenti, Siv Sivaloganathan

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Although the mechanisms responsible for elevated interstitial fluid pressure (IFP) in tumours remain obscure, it seems clear that high IFP represents a barrier to drug delivery (since the resulting adverse pressure gradient implies a reduction in the driving force for transvascular exchange of both fluid and macromolecules). R. Jain and co-workers studied this problem, and although the conclusions drawn from their idealized mathematical models offered useful insights into the causes of elevated IFP, they by no means gave a definitive explanation for this phenomenon. In this paper, we use poroelasticity theory to also develop a macroscopic mathematical model to describe the time evolution of a solid tumour, but focus our attention on the mechanisms responsible for the rise of the IFP, from that for a healthy interstitium to that measured in malignant tumours. In particular, we discuss a number of possible time scales suggested by our mathematical model and propose a tumour-dependent time scale that leads to results in agreement with experimental observations. We apply our mathematical model to simulate the effect of “vascular normalization” (as proposed by Jain in Nat Med 7:987–989, 2001) on the IFP profile and discuss and contrast our conclusions with those of previous work in the literature.

Original languageEnglish (US)
Pages (from-to)1172-1194
Number of pages23
JournalBulletin of Mathematical Biology
Volume80
Issue number5
DOIs
StatePublished - May 1 2018

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology
  • Mathematics(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Pharmacology
  • Agricultural and Biological Sciences(all)
  • Computational Theory and Mathematics

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