Abstract B30: Development of robust in vitro 3D models of human tumors for the identification and evaluation of anti-cancer drugs

Abstract

Abstract Currently in vivo testing of animals is still the gold standard for drug development and testing of cytotoxic compounds. With the demand for non-animal alternatives raising here we compared the development and functionality of two 3D culture models for tumor spheroids. Firstly 3D tumor spheroids were generated from lung cancer cell lines (NCI-H1650, NCI-H2170, NCI-H1975 and HCC-827) with known EGFR pathway mutations, and also primary isolated lung cancer epithelial cells, by encapsulation within an Alginate matrix to produced isogenic cell populations. Additionally, spheroids were co-cultured alongside primary Cancer-Associated Fibroblasts (CAFs). Following generation (7 days), spheroids (up to 500µm diameter) were treated with cytotoxic agents. The presence of CAFs attenuated the growth of smaller tumor spheroids (<100μm) although drug responses were not markedly changed in larger spheroids. Secondly, 3D tumor spheroids were generated using the OrganDot system (Asterand Biosciences) for the same lung and primary cell lines. Consistent responses were achieved between OrganDOT cultures and 3D alginate spheroids. Both systems allowed long-term viability of cultures allowing sequential or chronic compound testing. Both systems produced responses consistent with known genotypes for those cell lines. Ongoing studies using these models are focused at assessing whether anti-EGFR responses may predict the presence or absence of EGFR-pathway mutations in freshly isolated primary lung tumor cultures mutations. Citation Format: Amanda Carys Harvey, Graham Place, Kathryn Baggott, Satinder Samra, Caroline Freathy, Neil Cross. Development of robust in vitro 3D models of human tumors for the identification and evaluation of anti-cancer drugs [abstract]. In: Proceedings of the AACR International Conference: New Frontiers in Cancer Research; 2017 Jan 18-22; Cape Town, South Africa. Philadelphia (PA): AACR; Cancer Res 2017;77(22 Suppl):Abstract nr B30.