RESUMEN
We address the problem of determining from laboratory experiments the data necessary for a proper modeling of drug delivery and efficacy in anticancer therapy. There is an inherent difficulty in extracting the necessary parameters, because the experiments often yield an insufficient quantity of information. To overcome this difficulty, we propose to combine real experiments, numerical simulation, and Machine Learning (ML) based on Artificial Neural Networks (ANN), aiming at a reliable identification of the physical model factors, e.g. the killing action of the drug. To this purpose, we exploit the employed mathematical-numerical model for tumor growth and drug delivery, together with the ANN - ML procedure, to integrate the results of the experimental tests and feed back the model itself, thus obtaining a reliable predictive tool. The procedure represents a hybrid data-driven, physics-informed approach to machine learning. The physical and mathematical model employed for the numerical simulations is without extracellular matrix (ECM) and healthy cells because of the experimental conditions we reproduce.
Asunto(s)
Aprendizaje Automático , Preparaciones Farmacéuticas , Simulación por Computador , Modelos Teóricos , Redes Neurales de la ComputaciónRESUMEN
We couple a tumor growth model embedded in a microenvironment, with a bio distribution model able to simulate a whole organ. The growth model yields the evolution of tumor cell population, of the differential pressure between cell populations, of porosity of ECM, of consumption of nutrients due to tumor growth, of angiogenesis, and related growth factors as function of the locally available nutrient. The bio distribution model on the other hand operates on a frozen geometry but yields a much refined distribution of nutrient and other molecules. The combination of both models will enable simulating the growth of a tumor in a whole organ, including a realistic distribution of therapeutic agents and allow hence to evaluate the efficacy of these agents.
Asunto(s)
Melanoma/metabolismo , Melanoma/patología , Modelos Biológicos , Proliferación Celular , Matriz Extracelular/metabolismo , Melanoma/irrigación sanguínea , Neovascularización Patológica , Nutrientes/farmacocinética , Distribución Tisular , Microambiente TumoralRESUMEN
A continuum porous media model is developed for elucidating the role of the mechanical cues in regulating tumor growth and spreading. It is shown that stiffer matrices and higher cell-matrix adhesion limit tumor growth and spreading toward the surrounding tissue. Higher matrix porosities, conversely, favor the growth and the dissemination of tumor cells. This model could be used for predicting the response of malignant masses to novel therapeutic agents affecting directly the tumor microenvironment and its micromechanical cues.
