Abstract
Cancer is the most common cause of death in adult dogs. Many features of spontaneously developing tumors in pet dogs contribute to their potential utility as a human disease model. These include similar environmental exposures, similar clonal evolution as it applies to important factors such as immune avoidance, a favorable body size for imaging and serial biopsy, and a relatively contracted time course of disease progression, which makes evaluation of temporal endpoints such as progression free or overall survival feasible in a comparatively short time frame. These criteria have been leveraged to evaluate novel local therapies, demonstrate proof of tumor target inhibition or tumor localization, evaluate potential antimetastatic approaches, and assess the efficacy, safety and immune effects of a variety of immune-based therapeutics. Some of these canine proof of concept studies have been instrumental in informing subsequent human clinical trials. This review will cover key aspects of clinical trials in dogs with spontaneous neoplasia, with examples of how these studies have contributed to human cancer therapeutic development.
Highlights
Common concerns with regard to the clinical applicability of many murine models of human cancer include immune status, significantly reduced clonal heterogeneity, relative tumor burden, tumor location, species-specific differences in drug distribution/metabolism, and differences in in vivo drug concentrations that are achievable, among others
This large cancer burden in dogs indicates a group of spontaneously occurring tumors, many of which are histologically similar to human tumors
These important attributes have allowed the preclinical evaluation of novel cancer therapeutics that fall into several broad categories: [1] Local therapy approaches such as surgery, radiation therapy and locally-delivered drug therapy; [2] Proof of target inhibition and proof of tumor targeting; [3] Studies in the minimal residual disease setting; [4] Immunotherapy studies
Summary
Many features of spontaneously developing tumors in pet dogs contribute to their potential utility as a human disease model These include similar environmental exposures, similar clonal evolution as it applies to important factors such as immune avoidance, a favorable body size for imaging and serial biopsy, and a relatively contracted time course of disease progression, which makes evaluation of temporal endpoints such as progression free or overall survival feasible in a comparatively short time frame. These criteria have been leveraged to evaluate novel local therapies, demonstrate proof of tumor target inhibition or tumor localization, evaluate potential antimetastatic approaches, and assess the efficacy, safety and immune effects of a variety of immune-based therapeutics.
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