Abstract
Simple SummaryLaboratory rodents are the most common animal models used in preclinical cancer research. Companion animals with naturally occurring cancers are an under-utilized natural model for the development of new anti-cancer drugs. Dogs and cats develop several types of cancers that resemble those arising in humans with similar clinical and histopathological features and often with similar molecular and genetic backgrounds. Exposure to environmental carcinogens, including air, food and water are also common between people and their pets. Dogs and cats are a unique model that could be integrated between the preclinical laboratory animal model and human clinical trials.Companion animals with naturally occurring cancers can provide an advantageous model for cancer research and in particular anticancer drug development. Compared to commonly utilized mouse models, companion animals, specifically dogs and cats, share a closer phylogenetical distance, body size, and genome organization. Most importantly, pets develop spontaneous, rather than artificially induced, cancers. The incidence of cancer in people and companion animals is quite similar and cancer is the leading cause of death in dogs over 10 years of age. Many cancer types in dogs and cats have similar pathological, molecular, and clinical features to their human counterparts. Drug toxicity and response to anti-cancer treatment in dogs and cats are also similar to those in people. Companion animals share their lives with their owners, including the environmental and socioeconomic cancer-risk factors. In contrast to humans, pets have a shorter life span and cancer progression is often more rapid. Clinical trials in companion animals are cheaper and less time consuming compared to human trials. Dogs and cats with naturally occurring cancers are an ideal and unique model for human cancer research. Model selection for the specific type of cancer is of pivotal importance. Although companion animal models for translational research have been reviewed previously, this review will try to summarize the most important advantages and disadvantages of this model. Feline oral squamous cell carcinoma as a model for head and neck squamous cell carcinoma and canine oral melanoma as a model for mucosal melanoma and immunotherapy in people will be discussed as examples.
Highlights
Companion animals with naturally occurring cancers can provide an advantageous model for cancer research and in particular anticancer drug development
Preclinical cancer research is mainly based on laboratory animal models with most of the studies performed on tumors grown in rodents [1]
Experiments conducted in caged laboratory animals can be affected by high levels of stress that could affect the response to investigational drugs and immunotherapy
Summary
FOSCC and HNSCC have similar histological appearances with common dysregulated pathways and molecular markers [45,52,53]. The epithelial growth factor (EGF) signaling pathway involved in the cancer development, progression, metastasis, and angiogenesis, is dysregulated in many cancers [55]. EGFR is overexpressed in a large proportion of FOSCC, but the prognostic significance is still controversial [17]. High Cox-2 expression is found in a large proportion of HNSCC, and overexpression is considered a negative prognostic factor [57]. Increased expression can be correlated with poor prognosis in people [62,63] and in one study in cats, and COX-2 and VEGF expression were correlated with FOSCC disease progression [64]. High levels of BMI-1 have been found in both FOSCC and HNSCC with possible prognostic implication and future new treatment avenues in both cancers [71,72]
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