We are working on establishing reliable assays for in vitro screening of cancer drug sensitivity based on a tumor culture model system that employs semi-synthetic hydrogels. The 3D culture conditions in the hydrogels better mimic the normal conditions of tumor growth in vivo, enabling more reliable testing methodologies for determining quantitative chemo-sensitivity and optimal drug dosing.
A major challenge facing the field of in vitro drug screening is the lack of reliable tumor model systems for evaluation of drug potency and patient-specific chemosensitivity. Our laboratory has been developing an in vitro tumor growth system that uses a simple approach to quantify the chemosensativity and the optimal drug dosing for malignant tumors. The system works by cultivating a tumor biopsy in our semi-synthetic PEG-fibrinogen (PF) hydrogel materials for up to 6 days and documenting tumor cell migration. The PF hydrogel was capable of supporting the progressive expansion of the tumor biopsy in vitro in a 3D milieu that is specifically designed to selectively enhance malignant cell migration from the tumor biopsy, while limiting mesenchymal cell outgrowth. In addition, the matrix is transparent, enabling straightforward monitoring of in vitro malignant cell progression using simple, non-invasive optical techniques. Quantitative cell outgrowth data shows a linear relationship between tumor cell outgrowth and culture time, with significantly different outgrowth kinetics for tumor cells compared to mesenchymal cells. The presence of anticancer drugs in the culture medium, including doxorubicin and cisplatin, inhibited the tumor cell outgrowth kinetics in a dose dependent manner, thus enabling straightforward verification of chemosensitivity. Taken together, these results confirm that our tumor culture system is able to effectively assay chemosensitivity of tumor biopsies using straightforward and practical techniques.
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