Murine cancer models have been extremely useful for analyzing the biology of pathways involved in cancer initiation, promotion, and progression. However, they frequently do not adequately represent many of the features that define cancer in humans, including long periods of latency, genomic instability, and the heterogeneity of both tumor cells and their surrounding microenvironment. Most importantly, the complex biology of cancer recurrence and metastasis, integral to outcomes in human patients, are not appreciably reproduced in the conventional mouse models used in cancer drug development. Furthermore, in many cases, there has been inadequate consideration of relevant exposures for new drugs that are evaluated in mice. The development and approval of novel cancer drugs is lengthy and expensive 
; therefore, additional models that better represent the human disease are needed.
Current drug development pathways are frequently unidirectional. Novel agents are assessed in conventional preclinical models of efficacy and toxicity before moving into human clinical trials where they either fail or succeed. Particularly with novel targeted therapies the conventional paradigms of toxicity studies conducted in healthy animals followed by Phase I and Phase II human trials leave unanswered many important questions on the “best use” of these drugs 
. Translational drug development studies in pet dogs with cancer provide an opportunity to answer these questions by serving as an intermediary between conventional preclinical models and human clinical trials 
. In these dogs, cancers develop naturally in the context of an intact immune system and with a syngeneic host and tumor microenvironment. Similar environmental, nutrition, age, sex, and reproductive factors lead to tumor development and progression in human and canine cancers. They share similar features such as histologic appearance, tumor genetics, biological behavior, molecular targets, therapeutic response, and unfortunately, acquired resistance, recurrence, and metastasis.
Clinical trials in pet dogs are not constrained by traditional Phase I, Phase II, and Phase III trial designs. This allows novel agents to be offered to pet dogs before conventional therapies or during the period of minimal residual disease. Pet owners are highly motivated to seek novel options for management of cancer in their pets, especially if conventional treatments do not meet their goals. A pet owner's decision to pursue an investigational treatment is often influenced by the risks associated with this therapy compared to conventional therapy, as well as their expectations for outcomes and reduced costs for care provided by an investigational trial. Additionally, many pet owners are motivated by the opportunity to contribute to the advancement of cancer treatment for future human and canine patients.
The study of cancer biology and therapy in animals with naturally occurring cancers, referred to as comparative oncology, is not a novel concept. Indeed, over the last 30–40 years investigators have used this approach to make important contributions to the understanding and practice of human oncology in fields such as basic tumor biology and immunology 
, radiation biology 
, hyperthermia 
, and systemic therapies for a variety of cancers including osteosarcoma, lymphoma, melanoma, and others 
. One historical limitation to the widespread use and integration of the comparative approach has been a lack of infrastructure to coordinate animal health professionals with the human oncology community, drug developers, and basic scientists.