Three-Dimensional Cell Cultures in Anticancer Drug Researches: From Traditional Methods to Emerging Microfluidic Technology

Despite the expensive and time-consuming pre-clinical assessments, more than 50% of medicines fail to reach manufacturing cycle due to the low therapeutic index or possible side effects. Moreover, the challenge of drug resistance and person-to-person variation in complex diseases, such as cancer, and the growing concept of personalized medicine has also made a strong demand for more reliable pre-clinical drug assessment models. Cell culture is an essential and widely-used model in pre-clinical trials, but today we know that traditional culture methods fail to mimic the real in-vivo microenvironment, and hence they are proven to be responsible for the trails’ failure. It seems that the problem is going to be solved by the advent of three-dimentional (3D)-cell culture systems in which cell-cell and cell-matrix interaction, as well as the gradients of drugs, oxygen, metabolites, and nutrients, are well designed to efficiently mimic natural conditions, and provide more reliable results for drug assessments. A variety of researchers have purposed that this new paradigm, either directly or indirectly (by affecting gene expression and inducing natural phenotypes), affect cell behavior to meet the challenge of pre-clinical and clinical inconsistency. Recently, 3D-cultures on microfluidic platforms are used to provide a higher level of adaptation to living bodies. Due to the comparable similarity between microchips and living cells scales as well as the body vessels, besides the possibility to run a dynamic culture situation with real physical tension, etc. they are more potent to mimic actual in vivo microenvironment. Therefore, here, we are going to review various models of 3D-cell culture systems, and discuss their impact on pharmaceutical researches.