Abstract A104: Development of pathophysiologically relevant in vitro tumor models: Cytotoxicity of anticancer drugs in two dimensional and three dimensional cell line cultures versus primary colorectal tumor cells
Authors: Das Viswanath , Zbozinkova Marta , Holoubek Martin , Dzubak Petr , Hajduch Marian 
Published: May 2016

Chemotherapy is an effective modality for cancer therapy. However, treatment of solid tumors is hampered by several factors, such as development of acquired resistance, nonspecific drug effects, etc. Moreover, high attrition rate of anticancer drugs is an additional clinical hurdle often encountered in cancer patients. One of the potential ways to overcome these issues is to use in vitro tumor models that reliably capture in vivo tumor conditions for effective drug selection in the preclinical stages. Although two-dimensional (2D) cultures of cancer cells are widely used for drug screening and target validation; they are less predictive in vitro tumor models than three-dimensional (3D) cultures and primary cultures of patient-derived tumor cells. Cytotoxic drugs, nanoparticles, and antitumor antibodies display altered activity in 2D, 3D, and primary cancer cell cultures, potentially due to cellular and molecular differences in these culture types. Recently, the use of multicellular 3D spheroid cultures of cancer cells have gained considerable attention among researchers as more predictive in vitro tumor models to study the effects of tumor microenvironment on cancer cell response to drugs. In addition to 3D cultures, patient-derived tumor cells are also becoming increasingly popular in drug research for their relative closeness to tumors. It is expected that drugs characterized using these pathophysiologically relevant in vitro tumor models will improve their translation to higher disease models, and significantly reduce the cost associated with failure of drugs in the clinical trials.

In this study, we compare the cytotoxic effects of 12 standard anticancer drugs in 2D and 3D cultures of colorectal carcinoma (CRC) cells to &gt;500 primary CRC cultures. Furthermore, using primary cultures of patient-derived ovarian, breast, and lung cancer cells, we present the potential use of primary tumor cells as in vitro predictive model for chemotherapy. Our data indicates that compared to 2D cultures, 3D cultures of CRC cells better reflect the drug effects seen in primary CRC cultures. Our cytotoxicity data from primary cultures also show how the drug sensitivity profiles differ across histologically different solid tumors types.

Acknowledgements

This work was supported by grants from the Czech Ministry of Education, Youth and Sports (CZ.1.07/2.3.00/30.0041 to V.D.; LO1304 to M.H.), the Czech Ministry of Health (NT14282 to M.H.), and the Technological Agency of the Czech Republic (TE01020028 to M.H.).

Citation Format: Viswanath Das, Marta Zbozinkova, Martin Holoubek, Petr Dzubak, Marian Hajduch. Development of pathophysiologically relevant in vitro tumor models: Cytotoxicity of anticancer drugs in two dimensional and three dimensional cell line cultures versus primary colorectal tumor cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A104.