Cancer models in preclinical research: A chronicle review of advancement in effective cancer research

Abstract

Cancer is a major stress for public well-being and is the most dreadful disease. The models used in the discovery of cancer treatment are continuously changing and extending toward advanced preclinical studies. Cancer models are either naturally existing or artificially prepared experimental systems that show similar features with human tumors though the heterogeneous nature of the tumor is very familiar. The choice of the most fitting model to best reflect the given tumor system is one of the real difficulties for cancer examination. Therefore, vast studies have been conducted on the cancer models for developing a better understanding of cancer invasion, progression, and early detection. These models give an insight into cancer etiology, molecular basis, host tumor interaction, the role of microenvironment, and tumor heterogeneity in tumor metastasis. These models are also used to predict novel cancer markers, targeted therapies, and are extremely helpful in drug development. In this review, the potential of cancer models to be used as a platform for drug screening and therapeutic discoveries are highlighted. Although none of the cancer models is regarded as ideal because each is associated with essential caveats that restraint its application yet by bridging the gap between preliminary cancer research and translational medicine. However, they promise a brighter future for cancer treatment.

Keywords: cancer cell lines; computational cancer models; genetically engineered mouse models; organoids; patient‐derived xenografts; personalized medicine.

FIGURE 1

Advancement in cancer research models

FIGURE 2

Development of cancer models. A, Representation of organoid cancer model development in artificial culture media by taking tumor cells from a cancer patient. B, Illustration of cancer cell lines grown in artificial culture media and its transplantation in immunocompetent mice. C, Mutated larval brain transplantation in the abdomen of female flies is shown to make the Drosophila Melanogaster model for cancer. D, Patient‐derived xenografts (PDXs) are developed by tumor cells that are derived from patients and transplanted into immunocompromised mice subcutaneously, orthotopically, or into the renal capsule. E, Zebrafish can be utilized in cancer studies either by the alternating nucleotide sequence of DNA or by the PDXs approach in which cancer tumor cells are developed from isolated or resected patient material and are introduced into larvae of zebrafish. F, Genetically Engineered Mouse Models are developed by altering the hereditary profile of the mice to an extent that genes involved in transformation are overexpressed, replaced, or deleted. G, Illustration of pig cancer model development is shown by infecting transgenic oncopig with AdCre to induce removal of STOP codon for expression of transgene and tumors at the site of injection. H, Computational cancer models are generated when omics data are generated from initial in vivo and in vitro experiments and are utilized to develop the process of computational tools. These tools involve the steps of parameter estimation, stimulation of drugs, prediction, validation, and model refinement

FIGURE 3

Application of cancer models in various cancer. Experimental models are being used to determine the characteristics of the different types of tumor proliferating in different organs inside the body. Despite the limitations and advantages of these models, each type of cancer growth associated with a particular organ (eg, lungs, breast, ovarian) interacts and responds to these experimental models differently. The following pictorial representation indicates the cancer model application and shows which experimental model depicts the properties of a specific cancer type more successfully than the other