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Pharmacodynamics modeling based on in vitro 2D cell culture experiments

With the advancement of technology and medicine, personalized therapies arise which may provide a promising solution for the problems of chemotherapy, such as many side effects. Personalized therapies can be applied that meet the individual needs of patients, this can make the healthcare of cancer patients safer and more cost-effective. However, personalized therapy requires a reliable model of tumor dynamics and the effect of the drug applied during the therapy. Examining the effect of certain drugs on in vitro cell cultures helps us to gain understanding of the drug mechanism and create pharmacodynamics models. In vitro experiments provide a more cost-effective, ethical and more controllable way to examine the effect of chemotherapeutic agents. In this work, we carried out parameter identification and validation of several versions of a tumor growth model based on in vitro cytotoxicity measurements in two-dimensional tumor cell cultures. In vitro experiments were carried out on Brcal– / –; p53 mice breast cancer cell line. The chemotherapeutic agents used were Doxil and Doxorubicin at different concentrations. Parameter identification was performed by fitting to data measured at 12 time points in 5 days. We examined how the presence or absence of necrotic rate n and an additional Hill coefficient affect the value of sum square error (SSE). We showed that the models that contain tumor cell necrosis and a general Hill function have the best performance for Doxil.