We propose a mathematical model to describe enzyme-based tissue degradation in cancer therapies. The proposed model combines the poroelastic theory of mixtures with the transport of enzymes or drugs in the extracellular space. The effect of the matrix degrading enzymes on the tissue composition and its mechanical response are accounted for. Numerical simulations in 1D, 2D and axisymmetric (3D) configurations show how an injection of matrix degrading enzymes alters the porosity of a biological tissue. We eventually exhibit numerically the main consequences of a matrix degrading enzyme pretreatment in the framework of chemotherapy: the removal of the diffusive hindrance to the penetration of therapeutic molecules in tumors and the reduction of interstitial fluid pressure which improves transcapillary transport. Both effects are consistent with previous biological observations.
The definition of an innovative therapeutic protocol requires the fine tuning of all the involved operations in order to maximize the efficiency. In some cases, the price of the experiments, or their duration, represents a great obstacle and the full potential of the protocol risks to be reduced or even hidden by a non-optimal application.The implementation of a numerical model of the protocol may represent the solution, allowing a systematic exploration of all the different alternatives, shedding the light on the most promising combination and also identifying the key elements/parameters.In this paper, the injection of a plasmid, preceded by a hyaluronidase injection, is simulated through a mathematical model. Some key elements of the administration protocol are identified by means of a mathematical optimization procedure, maximizing the efficacy of the therapy. As a side effect of the extensive investigation, robust solutions able to reduce the effects of human errors in the administration are also obtained.
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