Pre-Clinical In Vitro Models Used in Cancer Research: Results of a Worldwide Survey

SIMPLE SUMMARY: Cancer cell lines, grown on plastic dishes i.e., two-dimensional (2D), are routinely used in cancer research, e.g., when evaluating the effectiveness of potential anti-cancer drugs before proceeding to studies in animal models and then human clinical trials. Stop/go decisions are generally made from these initial studies. As only ~10% of potential anti-cancer drugs succeed during clinical development, this suggests that these models are inadequate. Cells grown as three-dimensional (3D) models, akin to a tumor mass and with other cells that would naturally occur in its environment, should be more clinically relevant. We performed a worldwide survey, open to cancer researchers at all stages and in all settings, to find out what models they use; for what purposes, and why they chose those models. The majority reported using 2D models only, mainly due to lack of experience and costs but expressed interest in 3D cultures. Guidelines on how to develop such models cost-effectively are needed. ABSTRACT: To develop and subsequently get cancer researchers to use organotypic three-dimensional (3D) models that can recapitulate the complexity of human in vivo tumors in an in vitro setting, it is important to establish what in vitro model(s) researchers are currently using and the reasons why. Thus, we developed a survey on this topic, obtained ethics approval, and circulated it throughout the world. The survey was completed by 101 researchers, across all career stages, in academia, clinical or industry settings. It included 40 questions, many with multiple options. Respondents reported on their field of cancer research; type of cancers studied; use of two-dimensional (2D)/monolayer, 2.5D and/or 3D cultures; if using co-cultures, the cell types(s) they co-culture; if using 3D cultures, whether these involve culturing the cells in a particular way to generate spheroids, or if they use additional supports/scaffolds; techniques used to analyze the 2D/2.5D/3D; and their downstream applications. Most researchers (>66%) only use 2D cultures, mainly due to lack of experience and costs. Despite most cancer researchers currently not using the 3D format, >80% recognize their importance and would like to progress to using 3D models. This suggests an urgent need to standardize reliable, robust, reproducible methods for establishing cost-effective 3D cell culture models and their subsequent characterization.