Model description:
Consider the model from Dynamic Model of Tumor Growth (1). The complete model formulation describes the phenomenology of tumor growth slowdown, as the tumor consumes its available support; stimulatory and inhibitory influences from the tumor cells; inhibition due to administered inhibitors; and the clearance of the administered inhibitor. In the simplified model, the latter effect is not described, only the serum level of the inhibitor to be maintained is represented, so a second-order system is to be analyzed:
$$\begin{align*} \dot{x}_{1} &=-\lambda x_{1}\ln\left(\dfrac{x_{1}}{x_{2}}\right) \\ \dot{x}_2 &= b_x1 - dx_1^{{2}\over{3}}x_2 - ex_2u \\ y&=x_1, \end{align*}$$
where $x_1$ is the tumor volume (mm$^3$), $x_2$ is the vasculature volume (mm$^3$), and $u$ is the serum level of the inhibitor (mg/kg). The last equation represents that tumor volume is the measured output of the system. The characteristics of the parameters for the Lewis lung carcinoma and the mice used in the experiment are: $\lambda = 0.192($day$^{-1})$, $b = 5.85 ($day$^{−1}),$ $d =0.00873 ($day$^{−1}$mm$^{−2}),$ while the parameter characteristic for the inhibitor (endostatin) is: $e = 0.66 ($day$^{−1} ($mg/kg$)^{−1}).$ Attached figure shows the nonlinear behavior of the simplified model.
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Publication details:
| Title | Model-based Angiogenic Inhibition of Tumor Growth using Feedback Linearization |
| Publication Type | Conference Paper |
| Year of Publication | 2013 |
| Authors | Szeles, A., Drexler D.A., Sapi J., Harmati I., and Kovacs L. |
| Conference Name | IEEE 52nd Annual Conference on Decision and Control (CDC), 2013 |
| Date Published | 12/2013 |
| Publisher | IEEE |
| Conference Location | Firenze |
| ISBN Number | 978-1-4673-5714-2 |
| Accession Number | 14158507 |
| Keywords | cancer, feedback, linearisation techniques, medical control systems, nonlinear control systems, patient treatment, time-varying systems, tumours |
| Abstract | 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. |
| DOI | 10.1109/CDC.2013.6760184 |
