3.3 Lack of robust model system
Most of the preliminary studies are done on in-vitro 2D monolayer culture which may not show resemblance with an in-vivo tumor model. (Lovitt et al. , 2014). In artificial 2D mono-layer, cells spread on the plastic surface for several years can lead to accumulation of genetic aberrations with increasing passage number. Due to this, undefined mutation can result in loss of the characteristics of that tumor type or parental cancer cell. Besides they don’t engage in efficient cell-cell and cell-matrix interactions, and are devoid of tumor microenvironment (Katt et al. , 2016). All of these factors influence gene expression and protein function in 2D monolayer culture.Nearly half of chemo preventive agents fail in clinical testing, despite good results when tested on 2D in- vitro preclinical models.
Generation of animal transgenic tumor model or patient derived tumor Xenografts (PDTXs) are very expensive and time consuming. In toxicity related experiments animals are not good candidates for predicting human clinical outcome (Knight, 2008). The histological complexity and genetic heterogeneity of patient tumors are typically not reflected in engineered animal models. So there is great need to discover reliable 3Din-vitro culture model for predicting advance stages of drug activity in their discovery and developmental stage (Wong et al. , 2012). 3D spheroids in-vitro models almost mimic anin-vivo tumor environmental condition and it can be a model of choice to study phytochemical efficacy. It will also reduce the cost and time of failed clinical trials.