Cancer is one of the most destructive and lethal illnesses of the modern civilization. In the last decades, clinical cancer research shifted towards molecular targeted therapies which have limited side effects in comparison to conventional chemotherapy and radiation therapy. Anti-angiogenic therapy is one of the most promising cancer treatment methods. The dynamical model for tumor growth under angiogenic stimulator/inhibitor control was posed by Hahnfeldt et al. (1999), and it was investigated and partly modified many times. In this paper, a modified version of the originally published model is used in order to describe a continuous infusion therapy. To generalize individualized therapies a robust control method is proposed using H ∞ methodology. Uncertainty weighting functions are determined based on the real pathophysiological case and simulations are performed on different tumor volumes to demonstrate the robustness of the proposed method.

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Cancer is one of the most destructive and lethal illnesses of the modern civilization. In the last decades, clinical cancer research shifted towards molecular targeted therapies which have limited side effects in comparison to conventional chemotherapy and radiation therapy. Anti-angiogenic therapy is one of the most promising cancer treatment methods. The dynamical model for tumor growth under angiogenic stimulator/inhibitor control was posed by Hahnfeldt et al. (1999), and it was investigated and partly modified many times. In this paper, a modified version of the originally published model is used in order to describe a continuous infusion therapy. To generalize individualized therapies a robust control method is proposed using H ∞ methodology. Uncertainty weighting functions are determined based on the real pathophysiological case and simulations are performed on different tumor volumes to demonstrate the robustness of the proposed method.

In the last decades beside conventional cancer treatment methods, molecular targeted therapies show prosperous results. These therapies have limited side-effects, and in comparison to chemotherapy, tumorous cells show lower tendency of becoming resistant to the applied antiangiogenic drugs. In clinical research, antiangiogenic therapy is one of the most promising cancer treatment methods. Using a simplified model of the reference dynamical model for tumor growth under angiogenic inhibition from the literature, exact linearization is performed in the paper to handle the nonlinear behavior of the model. Two different control methods are applied on the linearized model: flat control and switching control. Simulations are performed on the nonlinear model to show the characteristics of the therapies carried out using the presented control methods.

Abstract-Cancer fighting treatments are expanding, and a promising type, targeted molecular therapies have a new approach. The aim of these therapies is not to eliminate the whole tumor, but to control the tumor into a given state and keep it there. Explicit knowledge of tumor growth dynamics and the effects of targeted molecular therapies is crucial in tumor treatment development. We show the results of mouse experiments where tumor growth was investigated in case of C38 colon adenocarcinoma and B16 melanoma. Several curves were fitted and tumor growth dynamics was examined. Three attributes of tumor were measured: tumor volume, tumor mass and vascularization; and tumor growth dynamics was examined. Tumor volume was measured with digital caliper, vascularization was investigated with CD31 antibody immunohistochemistry staining on frozen sections. The relationship between these tumor attributes were examined with linear regression analysis. The dynamics of tumor growth was identified as a second order linear system.