DEVELOPING A -3-DIMENTIONAL CO- CULTUERD CELLULAR MODEL FOR PERSONALIZED ANTI-CANCER DRUG SCREENING

Screening of anti-cancer drug activity is being performed predominantly in cultured tumor cells using monolayer cellular models, while in-vivo models are being used as the next proof of concept stage. However,the standard monolayer based in-vitro models lack the presentation of complex cell-cell interactions, extra-cellular matrix, and effects of the tumor environment. As a result, often the two-dimensional cellular models provide false positive results that lead to unnecessary in-vivo or clinical usage of drugs. There is a need to develop more reliable and relevant physiological cellular models for drug-screening that would better predict the clinical outcomes. Moreover, these models should be further optimized to be adjusted per patient for personalized medicine.

Our hypothesis is that shifting from two-dimensional to three-dimensional cell models, which contain more components of the tumor microenvironment, could substantially improve the reliability of the assays and provide better prediction for drug success.

Co-cultured multicellular spheroids were developed as a model for anti-cancer drug screening. The preparation methods of the tumor spheroids were compared, and the optimal one was selected for further morphological and homogeneity optimization. The growth of co-cultured spheroids of tumor and endothelial cells were studied and the optimal ratio of cells were determined per tumor type. Histological examination of spheroids demonstrated organized cell architectures and initiation of vessel formation. We concluded that the organization of tumor and endothelial cells are tumor-type dependent, and that patient-derived tumor cells show different tendencies for spheroid formation. This finding can lay the basis for persenolized drug screening in cancer.