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.