Evolution of Tumor Model: From Animal Model of Tumor to Tumor Model in Animal

Abstract

Patient derived xenograft (PDX) is defined as a growth of patients' tumor in the xenograft setting. The evolution of cancer model in animal has a century old history. The most single reason that exerted the pressure on the traditional animal model of cancer to evolve to PDX is that the traditional models have not delivered as expected and traditional models have not predicted clinical success. In spite of well above 50 drugs developed and approved for oncology over the last several decades, there remains a nirking paucity of clinical success as a reminder that this war on cancer riding on the animal model is far from won. In a backbreaking attempt to analyze the failure, the limitation of the "model" system appeared to be the most rational cause of this shortcoming. It was more of a failure to test a drug rather than a failure to make a drug that stunted our collective growth and success in cancer research. PDX is the product of this age-old failure and its fitness is currently tested in virtually all organ-type solid tumors. This review will present and appraise PDX model in the context of its evolution, its future promise, its limitations and more specifically, the current content of PDX in different solid tumors including breast, lung, colorectal, prostrate, GBM, pancreatic, hepatocellular carcinoma and melanoma.

Models used to screen for the treatment of multidrug resistant cancer facilitated by transporter-based efflux

“…Furthermore, the engraftment into an immunocompromised host has the potential to select for a more aggressive phenotype than originally present in the human patient (Marangoni et al 2007). The lack of an intact immune system in the immunocompromised murine host hinders the ability to study cancer-related immune responses in PDXs (Dey et al 2013;Malaney et al 2014). However, this limitation has been addressed with bioengineering approaches using GEMMs (discussed in the following section), immune cells and fibroblasts to establish an immunocompetent mouse model (Shultz et al 2012).…”

Using Pharmacogenomic Databases for Discovering Patient-Target Genes and Small Molecule Candidates to Cancer Therapy

“…Patient-derived tumor xenografts are potential complementary models for screening and development of anti-cancer agents in vivo ( Williams et al, 2013 ; Hidalgo et al, 2014 ). The proof of concept that it is possible to successfully apply PDXs as model has been provided in many large-scale pharmacogenomics PDX studies using various cancer types ( Dey et al, 2013 ; Hidalgo et al, 2014 ). The development of breast carcinoma subtypes-in-mouse PDX models has helped the identification of small chemical inhibitors to PI3K ( Lehmann et al, 2014 ), checkpoint kinase 1 ( Ma et al, 2012 ), aurora kinase ( Romanelli et al, 2012 ), BCL-2 family-BH3 mimetic ( Whittle et al, 2015 ), and many other drugs approved for treatment of breast cancers ( Zardavas et al, 2013 ).…”

3D bioprinting tumor models mimic the tumor microenvironment for drug screening

“…These animal tumor models are more similar to human pathology, but have limitations such as high costs, lengthy preparation times, low modeling success rates, species differences, and the inability to screen tumor immunotherapy-related drugs. 5,6 Two-dimensional monolayer tumor cell cultures are suspensions of cells or monolayers produced through cell culture, and this approach is one of the most frequently used for tumor drug screening because of its simplicity, high throughput, sensitivity, short time requirements, and quick analysis. Nonetheless, considerable differences are observed between the two-dimensional tumor cell model and actual human tumor cells in the three-dimensional dynamic microenvironment, which lacks cell-cell interactions and cell-extracellular matrix (ECM) interactions.…”