The Hele-Shaw asymptotics for mechanical models of tumor growth

TL;DR

This paper derives and analyzes a Hele-Shaw type free boundary model for tumor growth, starting from cell-level descriptions and including nutrient effects, with rigorous convergence and uniqueness results.

Contribution

It formulates a new Hele-Shaw asymptotic model for tumor growth from microscopic descriptions and provides detailed mathematical analysis including convergence and uniqueness.

Findings

Proved strong convergence to the Hele-Shaw limit.

Established uniqueness for the asymptotic problem.

Extended the model to include nutrient dynamics with new technical estimates.

Abstract

Models of tumor growth, now commonly used, present several levels of complexity, both in terms of the biomedical ingredients and the mathematical description. The simplest ones contain competition for space using purely fluid mechanical concepts. Another possible ingredient is the supply of nutrients through vasculature. The models can describe the tissue either at the level of cell densities, or at the scale of the solid tumor, in this latter case by means of a free boundary problem. Our first goal here is to formulate a free boundary model of Hele-Shaw type, a variant including growth terms, starting from the description at the cell level and passing to a certain limit. A detailed mathematical analysis of this purely mechanical model is performed. Indeed, we are able to prove strong convergence in passing to the limit, with various uniform gradient estimates; we also prove uniqueness for the asymptotic Hele-Shaw type problem. The main tools are nonlinear regularizing effects for certain porous medium type equations, regularization techniques \`a la Steklov, and a Hilbert duality method for uniqueness. At variance with the classical Hele-Shaw problem, here the geometric motion governed by the pressure is not sufficient to completely describe the dynamics. A complete description requires the equation on the cell number density. Using this theory as a basis, we go on to consider the more complex model including nutrients. We obtain the equation for the limit of the coupled system; the method relies on some BV bounds and space/time a priori estimates. Here, new technical difficulties appear, and they reduce the generality of the results in terms of the initial data. Finally, we prove uniqueness for the system, a main mathematical difficulty.