Animal models and therapeutic molecular targets of cancer: utility and limitations

Abstract

Cancer is the term used to describe over 100 diseases that share several common hallmarks. Despite prevention, early detection, and novel therapies, cancer is still the second leading cause of death in the USA. Successful bench-to-bedside translation of basic scientific findings about cancer into therapeutic interventions for patients depends on the selection of appropriate animal experimental models. Cancer research uses animal and human cancer cell lines in vitro to study biochemical pathways in these cancer cells. In this review, we summarize the important animal models of cancer with focus on their advantages and limitations. Mouse cancer models are well known, and are frequently used for cancer research. Rodent models have revolutionized our ability to study gene and protein functions in vivo and to better understand their molecular pathways and mechanisms. Xenograft and chemically or genetically induced mouse cancers are the most commonly used rodent cancer models. Companion animals with spontaneous neoplasms are still an underexploited tool for making rapid advances in human and veterinary cancer therapies by testing new drugs and delivery systems that have shown promise in vitro and in vivo in mouse models. Companion animals have a relatively high incidence of cancers, with biological behavior, response to therapy, and response to cytotoxic agents similar to those in humans. Shorter overall lifespan and more rapid disease progression are factors contributing to the advantages of a companion animal model. In addition, the current focus is on discovering molecular targets for new therapeutic drugs to improve survival and quality of life in cancer patients.

Keywords: cats; companion animal cancer model; dogs; molecular targets; mouse cancer model.

Figure 1

Importance of companion animal cancer models during drug discovery for cancer detection and treatment. Note: Complexity of cancer models ranging from in vitro to in vivo models and correlation with their utility during the novel therapeutic and imaging agents’ evaluation.

Figure 2

Phylogenic trees of genes for different species. Notes: Phylogenetic trees of several cancer-related genes. (A) p53, (B) c-Myc, (C) COX-2, and (D) c-KIT/CD117, show that dog and cat genes are more similar to human genes when compared with those of the mouse. Sequence homology was compared using the Basic Local Alignment Search Tool from the National Center for Biotechnology Information and the phylogenetic trees were constructed based on the COBALT Multiple Sequence Alignment Tool with “neighbor joining” as the tree construction method. Abbreviations: c-KIT/CD117, tyrosine-protein kinase Kit/cluster of differentiation 117; c-Myc, cellular myelocytomatosis oncogene; COX-2, cyclooxygenase-2; p53, tumor suppressor p53.