Creation of an NCI comparative brain tumor consortium: informing the translation of new knowledge from canine to human brain tumor patients

Abstract

On September 14-15, 2015, a meeting of clinicians and investigators in the fields of veterinary and human neuro-oncology, clinical trials, neuropathology, and drug development was convened at the National Institutes of Health campus in Bethesda, Maryland. This meeting served as the inaugural event launching a new consortium focused on improving the knowledge, development of, and access to naturally occurring canine brain cancer, specifically glioma, as a model for human disease. Within the meeting, a SWOT (strengths, weaknesses, opportunities, and threats) assessment was undertaken to critically evaluate the role that naturally occurring canine brain tumors could have in advancing this aspect of comparative oncology aimed at improving outcomes for dogs and human beings. A summary of this meeting and subsequent discussion are provided to inform the scientific and clinical community of the potential for this initiative. Canine and human comparisons represent an unprecedented opportunity to complement conventional brain tumor research paradigms, addressing a devastating disease for which innovative diagnostic and treatment strategies are clearly needed.

Maximizing Local Access to Therapeutic Deliveries in Glioblastoma. Part V: Clinically Relevant Model for Testing New Therapeutic Approaches

“…Our efforts include the identification of pharmacologically tractable molecular targets common to human and canine brain tumors, as well as the development of novel macroscopic methods of CNS drug delivery that overcome the limitations imposed by the bloodbrain barrier (BBB) and blood brain tumor barrier (BBTB) (13,14). The design and conduct of clinical trials in dogs with naturally occurring brain tumors is a major mechanism by which we assess our drug and device discoveries (10,13).…”

“…The potential of companion animals, and particularly dogs, with naturally occurring cancers to provide answers to these questions is being increasingly recognized and realized (7)(8)(9)(10). A growing body of evidence indicates that several spontaneous canine cancers are clinically, phenotypically, and molecularly similar to their human analogs, thus providing unique avenues for preclinical discovery and testing (7,8,10).…”

“…The potential of companion animals, and particularly dogs, with naturally occurring cancers to provide answers to these questions is being increasingly recognized and realized (7)(8)(9)(10). A growing body of evidence indicates that several spontaneous canine cancers are clinically, phenotypically, and molecularly similar to their human analogs, thus providing unique avenues for preclinical discovery and testing (7,8,10). Translational studies of investigational agents in, for example, tumor-bearing dogs can provide a variety of pharmacokinetic, mechanistic, toxicity, and anti-tumor activity data in an immunocompetent host, and thus offer numerous opportunities to more accurately guide the drug development process (8)(9)(10).…”

“…A growing body of evidence indicates that several spontaneous canine cancers are clinically, phenotypically, and molecularly similar to their human analogs, thus providing unique avenues for preclinical discovery and testing (7,8,10). Translational studies of investigational agents in, for example, tumor-bearing dogs can provide a variety of pharmacokinetic, mechanistic, toxicity, and anti-tumor activity data in an immunocompetent host, and thus offer numerous opportunities to more accurately guide the drug development process (8)(9)(10). It has been suggested that inclusion of preclinical canine studies in the drug development pathway could result in billions of dollars of research savings, principally by improving the design of Phase II human clinical trials and thus potential avoidance of the historically high latestage failure and attrition rates of new cancer agents (9,11).…”

“…It has been suggested that inclusion of preclinical canine studies in the drug development pathway could result in billions of dollars of research savings, principally by improving the design of Phase II human clinical trials and thus potential avoidance of the historically high latestage failure and attrition rates of new cancer agents (9,11). Dogs with spontaneous brain tumors have been assimilated into several comparative neuro-oncology research programs in an effort to accelerate the development and translation of cancer drugs to the clinic, and to mutually improve the lives of dogs and humans with brain tumors (5,10,(12)(13)(14)(15).…”