I-Chi Lee* Pages 5407 - 5418 ( 12 )
The oncology pharmaceutical research spent a shocking amount of money on target validation and drug optimization in preclinical models because many oncology drugs fail during clinical trial phase III. One of the most important reasons for oncology drug failures in clinical trials may due to the poor predictive tool of existing preclinical models. Therefore, in cancer research and personalized medicine field, it is critical to improve the effectiveness of preclinical predictions of the drug response of patients to therapies and to reduce costly failures in clinical trials. Three dimensional (3D) tumor models combine micro-manufacturing technologies mimic critical physiologic parameters present in vivo, including complex multicellular architecture with multicellular arrangement and extracellular matrix deposition, packed 3D structures with cell–cell interactions, such as tight junctions, barriers to mass transport of drugs, nutrients and other factors, which are similar to in vivo tumor tissues. These systems provide a solution to mimic the physiological environment for improving predictive accuracy in oncology drug discovery.
This review gives an overview of the innovations, development and limitations of different types of tumor-like construction techniques such as self-assemble spheroid formation, spheroids formation by micro-manufacturing technologies, micro-dissected tumor tissues and tumor organoid. Combination of 3D tumor-like construction and microfluidic techniques to achieve tumor on a chip for in vitro tumor environment modeling and drug screening were all included. Eventually, developmental directions and technical challenges in the research field are also discussed. We believe tumor on chip models have provided better sufficient clinical predictive power and will bridge the gap between proof-of-concept studies and a wider implementation within the oncology drug development for pathophysiological applications.
Three dimensional (3D) tumor model, sphere formation, micro-manufacturing technologies, microfluidic system, tumor organoids, on chip.
Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan