Modeling Opportunities in Comparative Oncology for Drug Development

Abstract

Successful development of novel cancer drugs depends on well-reasoned scientific drug discovery, rigorous preclinical development, and carefully conceived clinical trials. Failure in any of these steps contributes to poor rates of approval for new drugs to treat cancer. As technological and scientific advances have opened the door to a variety of novel approaches to cancer drug discovery and development, preclinical models that can answer questions about the activity and safety of novel therapies are increasingly necessary. The advance of a drug to clinical trials based on information from preclinical models presupposes that the models convey informative data for future use in human patients with cancer. The study of novel cancer drugs using in vitro models is highly controllable, reproducible, relatively inexpensive, and linked to high throughput. However, these models fail to reproduce many of the complex features of human cancer. Mouse models address some of these limitations but have important biological differences from human cancer. The integration of studies using pet dogs with spontaneously occurring tumors as models in the development path can answer questions not adequately addressed in conventional models and is therefore gaining attention and interest in drug development communities. The study of novel cancer drugs in dogs with naturally occurring tumors allows drug assessment in a cancer that shares many fundamental features with the human cancer condition, and thus provides an opportunity to answer questions that inform the cancer drug development path in ways not possible in more conventional models.

Unleashing the power of comparative oncology models in nanomedicine research

“…Relevant outcomes of veterinary preclinical trials may include proof-of principle data to support further investigation, PK and PD data to guide dosing decisions, and elucidation of tumor targeting efficacy and drug safety. Access to these resources may be gained via contact through searchable veterinary clinical trials databases and through veterinary specialty organizations engaged in research (27)(28)(29). Examples are provided in Table 2.…”

The importance of comparative oncology in translational medicine

“…Dogs and humans often have the same responses to therapies, and therefore, studies in dogs may provide useful information about drug toxicity and the mechanisms underlying the resistance of human patients to chemotherapy. There is no "gold standard" treatment for many canine cancers and so it is possible to evaluate new agents as firstline therapies, in combination with other treatments, or as adjunctive therapies in an expedited and efficient manner [41]. Moreover, as several cancer-associated genetic alterations that influence cancer progression in humans have been identified in canine cancer [36,42,43], testing new targeted therapies for cancer treatment holds great translational value for proof-of-concept and proof-of-target efficacy.…”

Translational Research in Oncology: The Need of Additional In Vitro Preclinical Testing Methods for New Drugs

“…This criticism also applies to all of the aforementioned in vitro models on cytotoxicity, proliferation, and angiogenesis, as discussed by Gordon & Khanna [22], but this issue is of particular interest in regard to cell migration, because cell migration is a very sensitive behavioral function. The migratory activity of cells is a gradual response and thus differs from the binary, yes-or-no decision of death and survival.…”