A mechanical model of a growing solid tumor: implications for vascular collapse and drug transport

Abstract

The authors have developed a soft tissue model that predicts the mechanical response of a solid tumor to its host environment. The effects of leaky vessels, lack of functional lymphatics, and tissue growth due to cell division were incorporated as distributed parameters into a poroelastic continuum model. The resulting simulations chronicled the evolution of high fluid pressure and solid stress regions within the tumor interstitium as a function of both expansion and age. In this study, the authors focused on two different applications of the model. By determining regions of sufficiently high stress, the poroelastic solution was used to predict the onset of vascular instability as caused by cell proliferation. The second application of the mechanical model of cancer was towards understanding biological transport in the tumor system. Pharmacokinetic models were developed that incorporate high interstitial pore pressure and the fluid flux barrier as determined from the poroelastic pore pressure solution. Spatial and temporal distributions of macromolecular therapeutic agents were determined within the tumor-host system, and the resulting simulations revealed an age dependent response.