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.

Homologous Mutation to Human BRAF V600E Is Common in Naturally Occurring Canine Bladder Cancer—Evidence for a Relevant Model System and Urine-Based Diagnostic Test

“…The domestic dog can provide such a system. Due to the similarities in histology, biological responses and presentation, canine cancers have already provided important clinical information to improve detection and treatment of human cancers(17). Canine lymphomas and bladder carcinomas have been used to determine dosage levels and test new chemotherapeutic agents while osteosarcoma in dogs proved invaluable for improving treatment strategies that preserve patient limbs(18).…”

Heralding a new paradigm in 3D tumor modeling

“…Moreover, it is yet possible to incorporate the entire tumor ecosystem in 3D models. In vivo models, such as genetically induced mouse models of cancer, as well as companion animals with spontaneous neoplasms, will still be needed to complement 3D in vitro models to understand the natural history of cancer [195]. For example, in mouse models engineered with genetic aberrations, tumors arise de novo in the presence of a normal immune system and coevolve with an intact stroma; such a system enables the study of causative changes in tumor development and growth [196].…”

Unleashing the power of comparative oncology models in nanomedicine research

“…Some canine cancers that have been studied as models of analogous human disease include breast, prostate, bladder, and head and neck cancer, as well as osteosarcoma, lymphoma, and malignant melanoma (9, 10). These naturally-occurring neoplastic diseases in companion animals offer significant advantages over more traditional in vivo models of induced neoplastic disease including similarities in terms of etiology, heterogeneity, biological and metastatic behavior, and clinical response to therapy than does a cancer induced in a laboratory animal with an incompetent immune system (9)(10)(11)(12). Many of these advantages are outlined in Table 1.…”