Improving Cancer Drug Discovery by Studying Cancer across the Tree of Life

Abstract

Despite a considerable expenditure of time and resources and significant advances in experimental models of disease, cancer research continues to suffer from extremely low success rates in translating preclinical discoveries into clinical practice. The continued failure of cancer drug development, particularly late in the course of human testing, not only impacts patient outcomes, but also drives up the cost for those therapies that do succeed. It is clear that a paradigm shift is necessary if improvements in this process are to occur. One promising direction for increasing translational success is comparative oncology-the study of cancer across species, often involving veterinary patients that develop naturally-occurring cancers. Comparative oncology leverages the power of cross-species analyses to understand the fundamental drivers of cancer protective mechanisms, as well as factors contributing to cancer initiation and progression. Clinical trials in veterinary patients with cancer provide an opportunity to evaluate novel therapeutics in a setting that recapitulates many of the key features of human cancers, including genomic aberrations that underly tumor development, response and resistance to treatment, and the presence of comorbidities that can affect outcomes. With a concerted effort from basic scientists, human physicians and veterinarians, comparative oncology has the potential to enhance the cost-effectiveness and efficiency of pipelines for cancer drug discovery and other cancer treatments.

Keywords: cancer drug discovery; cross-species studies; evolutionary biology; veterinary oncology.

Fig. 1.

Comparative oncology helps overcome current barriers to drug discovery. (A) Challenges to cancer drug discovery include limited access to patient samples for testing, inadequate models to study the immune system and tumor microenvironment, and an absence of models that fully recapitulate inter- and intrapatient tumor heterogeneity. Integrating comparative oncology into the drug discovery process can overcome these challenges and may speed efforts to design and test therapies and treatment paradigms. (B) The current drug discovery process is highly inefficient, taking almost a decade and costing ∼$1 billion to reach an FDA approval. Adopting comparative approaches adds additional inputs to the pipeline in the form of improved models and more diverse patients, leading to more rapid results. (C) Robust implementation of comparative approaches will require 1) institutions to foster cross-disciplinary efforts in oncology; 2) a concerted effort to build tools to study cancer across species; and 3) collaborative partnerships with academia, government, and industry.