Despite 40 to 50 years of research, only one month of furthered survival has been accomplished in the context of aggressive human brain cancer treatment. In mouse models, treatment has made significant progress, but neither chemically induced, genetically engineered, nor xenografted tumors in mice are adequately reflective of human disorders - maybe because of varied biology, maybe because of the method of instigating tumors - there are many deficits. In steps the dog brain. The paralleled genetic expression, higher natural physiological similarity, and far more similar immune system and naturally pathology of brain tumors in dogs provides a logical basis for their models to be more useful to investigating human therapies.
The use of dogs carries with it plenty of issues, which need to be superiored prior to the initiation of their use:
Case numbers. Owners pick their own treatments, adding plenty of variables.
Owner finances. Also reduces case numbers.
Late stages of disease. Presentation of brain tumors to veterinarians happens way later in the tumorigenesis.
Surgical techniques. The financial backing and equipment is lacking in this area of animal medicine, for example in not using a live MRI.
Unknown natural history.
Treatment trials inhibited by inclusion criteria and measures of outcome. Many variables, including the want to euthanize - thus, markers of outcome may need to be size of the tumor, years without tumor progression, etc, instead of survival.
Nobody will ever go back to the dog if the model fails. Education is severely lacking. What treatments do we use now for canines? Anti-inflammatory/seizure medication as palliative care, surgery (which is different - not removal, but debulking), radiotherapy… those 3 primary/common measures cost $10,000 for one dog in a standard way to grand the dog maybe a year of life. Less common treatments include chemotherapy, which is not as common for brain tumors for several reasons, partly due to the blood-brain barrier:
Low concentrations in the CNS
Lack of specificity
But these reasons hold a higher potential to surpass than do surgery and radiotherapy.
The people whose investments are needed to press forward with canine models are often more in a hurry to get results than can be accomplished, but we must educate them.
The efficacy of convection enhanced delivery is being observed; deliver benign iron oxide nanoparticle pumping directly into the tumor. Heating of the particles, which are useful to image, combined with cetuximab, which is an FDA-approved human cancer treatment. The mouse model showed significantly slower growth using this therapy. A “necessary evil” safety trial was done on healthy dog to establish dosage. It was shown that drugs attached to nanoparticles would be likely to live in the brain for at least 30 days. Ten dogs-owner partnerships were sponsored to have a combination treatment: some surgical removal (to help make the 72-hour treatment worth it), and pumps with drug infusion. The results were promising - reduction of tumor size, feasibility, safety, maintenance of reduced tumor volume.
Bead-facilitated drug delivery is also interesting to scientists. Temozolamide, an alkylating agent, is approved in humans, but only something like 20% ends up in cerebrospinal fluid. A mouse xenograft model, canine cadaver model, and healthy canine model were established. Five clinical dogs were operated on - temozolamide-seeded beads were stereotactically inserted and repeatedly imaged. It looks like tumor shrinking is occuring, and people are next in line.
Nanoparticle delivered drug therapy fights some issues with toxic, but effective drugs due to uncontrolled, too-fast release. Nanoparticles, which target oxidized tumor mitochondria, were effective, and not only that, but the healthy dog model was minimally systemically impactful. Thus, feasibility was high. Doses are still being worked out before a clinical trial. The advantage of a systemically delivered (IV) drug is high.
A nanofiber lined catheter can be used to guide tumor growth, which generally follows white matter. There was no need for a safety study, since the therapy was completely inert. The tumor would be guided to grow into a reservoir to be treated, or evaluated, or removed. The potential and feasibility was relatively high in this therapy, and it is headed to humans, as well.
Summary! Dogs are a naturally occuring model. They have a place in step-wise novel therapy development. Safety studies are vital. Feasibility, safety, and a suggested efficacy are reasonable targets for clinical canine work. Dogs and humans get to be treated... it gets to be funded… there is plenty of outsourcing within these studies, to chemistry departments (for nanoparticles), for bioengineering departments (for devices), for pharmacology (for drug specifics), for human interest and protocol management (for translation)
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