Evaluating the influence of mechanical stress on anticancer treatments through a multiphase porous media model

Pietro Mascheroni, Daniela Boso, Luigi Preziosi, Bernhard A. Schrefler

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Drug resistance is one of the leading causes of poor therapy outcomes in cancer. As several chemotherapeutics are designed to target rapidly dividing cells, the presence of a low-proliferating cell population contributes significantly to treatment resistance. Interestingly, recent studies have shown that compressive stresses acting on tumor spheroids are able to hinder cell proliferation, through a mechanism of growth inhibition. However, studies analyzing the influence of mechanical compression on therapeutic treatment efficacy have still to be performed. In this work, we start from an existing mathematical model for avascular tumors, including the description of mechanical compression. We introduce governing equations for transport and uptake of a chemotherapeutic agent, acting on cell proliferation. Then, model equations are adapted for tumor spheroids and the combined effect of compressive stresses and drug action is investigated. Interestingly, we find that the variation in tumor spheroid volume, due to the presence of a drug targeting cell proliferation, considerably depends on the compressive stress level of the cell aggregate. Our results suggest that mechanical compression of tumors may compromise the efficacy of chemotherapeutic agents. In particular, a drug dose that is effective in reducing tumor volume for stress-free conditions may not perform equally well in a mechanically compressed environment.

Original languageEnglish (US)
Pages (from-to)179-188
Number of pages10
JournalJournal of Theoretical Biology
Volume421
DOIs
StatePublished - May 21 2017

Keywords

  • Cancer
  • Chemotherapy
  • Mathematical model
  • Mechanical compression
  • Tumor spheroids

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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