Abstract
Human cancer cell lines are an integral part of drug discovery practices. However, modeling the complexity of cancer utilizing these cell lines on standard plastic substrata, does not accurately represent the tumor microenvironment. Research into developing advanced tumor cell culture models in a three-dimensional (3D) architecture that more prescisely characterizes the disease state have been undertaken by a number of laboratories around the world. These 3D cell culture models are particularly beneficial for investigating mechanistic processes and drug resistance in tumor cells. In addition, a range of molecular mechanisms deconstructed by studying cancer cells in 3D models suggest that tumor cells cultured in two-dimensional monolayer conditions do not respond to cancer therapeutics/compounds in a similar manner. Recent studies have demonstrated the potential of utilizing 3D cell culture models in drug discovery programs; however, it is evident that further research is required for the development of more complex models that incorporate the majority of the cellular and physical properties of a tumor.
Highlights
The only procedures developed for whole cell-based screening assays were those utilizing a flat layer of cells attaching to various plastic substrata
The development of more biologically relevant in vitro tumor models may result in improved translation and a reduction in number of the animal models required in drug discovery programmes [4]
If drug/compound sensitivity against tumor cells is increased in 3D cultures, is there a greater dependence on the target in the 3D cellular system? Or, are there indirect influences on drug/compound activity in tumor cells propagated in 3D culture not observed against cells cultured in
Summary
The only procedures developed for whole cell-based screening assays were those utilizing a flat layer of cells attaching to various plastic substrata. The procedures in place for the development of drugs involve thorough evaluation of novel drug candidates in both pre-clinical and clinical phases. Through these drug development practices, the attrition rates of drug candidates for cancer are significant, being approximately 95% [3]. The development of more biologically relevant in vitro tumor models may result in improved translation and a reduction in number of the animal models required in drug discovery programmes [4]. We will examine the 3D models that have been successfully implemented in early stage compound screening and the future of in vitro cell-based assays in cancer drug discovery practices
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