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One Health
Published in Rebecca A. Krimins, Learning from Disease in Pets, 2020
Comparative medicine can provide insights and advances in fighting disease and improving health and increasing life span. For example, dogs are excellent models for studying respiratory cancers of humans because of their exposure to such things as in-home tobacco smoke, radon and asbestos.32 Cancer in companion animals is very common (estimates put canine cancer deaths at 40–50% of those over the age of 10 years), and remarkably similar to cancer in humans in many ways that mouse models cannot capture.39 This has brought significant attention to the value of spontaneous canine cancer in drug discovery and validation that can benefit companion animals as well as humans.39 This has been coined “comparative oncology”. By tapping into a comparative medicine approach—a One Health approach—we can greatly expand our understanding of diseases, and through clinical trials learn how effective therapies in animals can benefit humans, and vice versa.
Porcine cancer models: potential tools to enhance cancer drug trials
Published in Expert Opinion on Drug Discovery, 2020
Noah Robertson, Lawrence B. Schook, Kyle M. Schachtschneider
Canine cancer models are the basis of the NCI Comparative Oncology Program [7], where cancers that occur naturally in veterinary clinical patients are treated and studied as a clinical trial with the goal to translate and compare treatment responses to humans to aid in clinical trial success [8]. Since these cases are naturally occurring models, the clinical value is critically high sine the dog is receiving treatment can then help other similar dogs and human patients. Furthermore, patients may have additional attributes for a particular cancer that is difficult to replicate in the laboratory such as comorbidities, metastasis, and epigenetics [62]. The Comparative Oncology Program has proven invaluable due to its ability to determine specific treatment regimens for both client-owned dogs and human patients. The Comparative Oncology Program has 22 veterinary oncology clinics; however, since canine tumors develop spontaneously as observed in humans, the same limitations related to lengthy accrual times apply to canine clinical trials [63]. In addition, ethical considerations and the inability to experimentally induce tumors in dogs limits the benefits of canine tumor models.
Predictive modeling for cancer drug discovery using canine models
Published in Expert Opinion on Drug Discovery, 2020
Michael D. Lucroy, Mark A. Suckow
Spontaneous tumors in dogs continue to be an underutilized resource for human cancer drug development. The similarities between cancers arising in dogs and humans, along with the potential applications of comparative oncology to advance human healthcare, have been recognized for more than 40 years [28–33]. Over the past few decades, similarities in the biologic behavior of many cancers, including lymphoma, osteosarcoma, and hemangiosarcoma, have been well-documented. Following the completion of the canine genome project, mutational similarities between human and canine cancers continued to be revealed, further supporting the relevance of cancer-bearing pet dogs for drug development. Because there are recognized cancer predispositions in certain dog breeds, they may also serve as tools for identifying important druggable targets [34–36]. For example, German shepherd dogs, boxers, and golden retrievers are all at increased risk for visceral hemangiosarcoma versus other breeds; and Schnauzers and Scottish terriers are at increased risk for cutaneous melanoma [37,38]. While no single genetic factor likely accounts for breed differences in susceptibility to cancer, loss, or reduction of tumor suppressor expression is often cited as a potentially important factor [37,39]
Defining potency of CAR+ T cells: Fast and furious or slow and steady
Published in OncoImmunology, 2019
Ivan Liadi, Harjeet Singh, Gabrielle Romain, Badrinath Roysam, Laurence JN Cooper, Navin Varadarajan
New immunobiology is needed to help define a T-cell product suitable for infusion. The large number of tumor-associated antigens, designs of immunoreceptors, T-cell subset(s) to be modified is but a few of the variables that aggregate to define the therapeutic potential of genetically modified T cells. Mouse models of comparative oncology are not amenable to scale up, and do not always predict efficacy in human trials.