Dr. Deborah Knapp, DVM Interview – World Renowned TCC Researcher for Canines at Purdue University– "We Are Going to Combat TCC in 3 Global Ways.”
I had the privilege of speaking with Dr. Deborah Knapp, DVM from Purdue University about her research in Transitional Cell Carcinoma in canines. She is the Director of the Purdue University College of Veterinary Medicine’s Comparative Oncology program and world-renowned for her work in bladder cancer in canines. Her work is aimed at improving the therapeutic outlook for pets and people with bladder cancer by conducting clinical trials in pets. The invasive form of TCC is a type of cancer that is remarkably similar between dogs and humans. When clinical trials are open, Knapp and her team will treat 60-70 dogs with TCC per year, but depending on the year upwards to 120 dogs could be evaluated. The COVID pandemic has forced Dr. Knapp’s team to suspend some of their clinical trial efforts, but they are eager to return to full capacity.
Combatting TCC in 3 Global Ways
Dr. Knapp believes we are going to make progress combatting TCC in 3 global ways.
1) Prevention and Early Detection
2) Better Drugs
3) Personalized Medicine
Prevention and Early Detection
Dr. Knapp believes detecting TCC earlier will make a huge difference. Early results from studies suggest that if the cancer is found early, the odds of remission and survival could greatly improve, perhaps doubling. Her group is working towards publishing results of screening for TCC and early intervention.
Knapp is eagerly awaiting more information regarding a mutation in a gene called BRAF. She stated, “8% of all human cancers have a mutation in the BRAF gene. 80% of dogs with bladder cancer have the same BRAF mutation. It is not inherited in the DNA, but it is triggered by other genes or something the dogs are exposed to. These dogs are born with a normal BRAF gene. There is likely some other DNA variant that has not been identified yet which makes the dog susceptible to developing the BRAF mutation. It is possible that environmental exposure during the dog’s lifetime plus one or more DNA variants result in the BRAF mutation. This will require more study to sort out.”
In her research she has discovered a relationship between spaying/neutering a dog and TCC. Dogs that are spayed/neutered have twice the risk of developing TCC when compared to intact dogs. However, she still advocates spaying/neutering to decrease the risk of other cancers. “An intact, female dog has about a 25% chance of mammary cancer in their lifetime,” according to Dr. Knapp. Therefore, she still suggests working with your veterinarian to schedule a spay/neuter, and to discuss the age at which it will be done.
Better Drugs
Dr. Knapp clearly knows better drugs are needed to fight TCC. Purdue University is in a favorable position for researching cancer because there is a cancer center on site funded by the National Cancer Institute (NCI). According to Dr. Knapp, one of the strengths of the NCI is making new cancer drugs.
In the next few months, Dr. Knapp hopes to publish a study about a new drug that will help dogs with TCC that have a specific genetic mutation. While this will offer another option for treating dogs with bladder cancer, Knapp says the medicine will be cost prohibitive unless another form of the drug emerges. But the science learned from the study is expected to lead to other more affordable treatment options that target the same mutation.
Last year, a study lead by one of Dr. Knapp’s colleagues showed the anthrax toxin delivered in a targeted way and in a way that it would not have the usual harmful effects of anthrax, was able to reduce a bladder tumor in dogs by ~30% after one treatment cycle. Dr. Knapp told me “that study was a good first step, but more information is needed to incorporate it as a treatment. To use anthrax routinely in dogs, the protocol needs to be optimized. We need to know how much to give and how often while making sure the dosage is safe for the dog.” Another hurdle to overcome with anthrax is finding a reliable, scalable source of the toxin. It is currently being made by graduate students in a lab at Purdue. The lead investigator of that study is applying for additional funding to answer those questions. In case anthrax does not become commercially available in the near term, Dr. Knapp believes there are other treatments being studied that will also prove to be helpful.
Personalized Medicine
How do you understand which treatment will be most effective for which dog? This question is a driver for much of Dr. Knapp’s research. “Why do some dogs do really well with a treatment, while others do very poorly,” I discussed with Dr. Knapp. She has been working on sequencing the tumors. “100 different tumors could look the same to a pathologist in a lab. However, if you sequence the RNA and determine which genes are expressed, the tumors can be grouped into two different subtypes. These subtypes define how aggressively the cancer behaves (spreads or does not spread), how likely the dog is to respond to treatment, and how long the dog is likely to live. It is not cut-and-dry. There is overlap between the subtypes. With one subtype, metastasis developed rapidly in ~3 months versus several months to years with the other subtype, based on data our team was looking at recently. We are getting better at determining which group a given dog would fit in, but we need to work on how each individual dog is going to respond. Ultimately, we expect that this can be used to determine the most appropriate treatment option based on the subtype.”
Other Treatment Studies
“There are too many things to study and not enough time or money to study them. Literally, you can find 100’s of things that people think will work for bladder cancer,” stated Dr. Knapp. Many people want more studies on some of the holistic treatments. She has a colleague looking at CBD oil. The study is trying to determine safe dosages, if there is an anti-tumor effect, and if there is an anti-anxiety effect?
She voiced some caution with people trying unstudied and unproven treatments that are labeled as “natural” or “holistic” or found on the internet. Her concern is that although people want to try these treatments as an option to provide hope for their pet, she believes people need to be cautious that they do not harm their pet. “Unproven does not mean harmless.”
Dr. Knapp’s Treatment Protocol
Dr. Knapp believes the best approach to treating TCC is to “use one treatment until that stops working and then move on to another treatment. When I meet with the owner of a dog newly diagnosed with bladder cancer to discuss which medicines may be helpful, I discuss two main treatment options: 1) all oral medications (Piroxicam, piroxicam-like drugs, oral chemo drugs), or 2) a combination of oral and IV medications. The difference is if you use the combination of IV and oral medications, you have close to a 60% chance of dramatically shrinking the tumor if its frontline therapy.”
“You want to dramatically shrink the tumor if the dog’s symptoms are really bothersome, such as if the dog asks to go outside to urinate every hour, all night long. The other reason would be if the tumor is blocking the flow of urine and is life threatening. There are other dogs that have very few symptoms and are living a happy life. Plus, some pet owners do not want to or are unable to commit to frequent vet visits or cannot afford the IV medications.”
“NSAIDs such as Piroxicam are certainly an alternative. They are convenient, inexpensive and there is a 20% chance the drug will shrink the tumor or a 50-60% chance it will stop the tumor from growing for a while. Besides, the pet owner can always start with oral medications and do IV medications later. It is important to know that 15% of dogs, maybe more, will get an irritated stomach using Piroxicam. Pet owners might notice loss of appetite, unexplained vomiting, or dark tarry-looking stools. If that happens, it is important to stop the piroxicam. They can consult with their veterinarian about considering a milder NSAID. Piroxicam is probably the best if the dog can tolerate it, but if they can’t tolerate it and get a stomach ulcer, it obviously sets the dog back in terms of treatment.”
“There is generally no right or wrong answer when it comes to selecting which drugs to use. It depends on what the pet owner can do based on the number of vet visits, costs, and what would benefit the dog the most. Whichever treatment is started, if the tumor is not growing and the dog feels good, then we keep doing it. If the dog does not feel good or the tumor starts growing, we try a different treatment. You get the longest life expectancy if you are willing to change treatments one after another when a given treatment fails. My treatment decisions are based on measuring the tumor size with ultrasound, and looking for changes in the size over time, because symptoms do not always match. It is not an exact science, though.”
Identifying Treatment Failure?
I was enjoying my conversation with Dr. Knapp very much, wishing she had been Tigger’s oncologist. Wondering if things would have been different for my beautiful girl that has been gone for just over a year. I had to ask her a question about Tigger when it started going downhill for her. I was unable to determine when a given treatment was failing. I am hoping this information will help someone else that faces the same uncertainty. I always wanted to have information so that I could make the best decisions for my girl. My oncologist was doing an ultrasound at each chemotherapy visit. Once Tigger became incontinent, it became very difficult to do the ultrasound. There needs to be a certain amount of urine in the bladder for the ultrasound to show images of the bladder. At this point, I was in the dark and Tigger was feeling unwell. It all went downhill from there.
I asked Dr. Knapp, “how do you determine treatment failure if you can’t see the images with the ultrasound.” Here is what she does in that case. If she gets ready to perform an ultrasound on a dog with an empty bladder, the first thing she does is wait a few hours to see if the dog will produce more urine. She generally keeps the dog until the dog produces enough urine. If the dog is incontinent, she could sedate the dog, pass a catheter and put some saline in the bladder to get images with the ultrasound. That is not a risk-free procedure though, as there is a risk of puncturing something while passing the catheter. So the best approach is to try to measure the tumor without having to pass a catheter.
Study Hurdles
People frequently come to see Dr. Knapp and ask, “why don’t you study this?” while laying down a recent article. Clinical trials on TCC are frequently conducted at Purdue. Dr. Knapp is sought out by pet owners because they appreciate her expertise, they want to take advantage of a clinical trial to help science, and/or since most clinical trials are subsidized it provides them a treatment option that they might not be able to otherwise afford.
Clinical trials and studies are often expensive. The recently completed study for the new drug that is being published soon, took 3 years to complete as they had to pass a scope into the bladder to obtain a sample of the tumor at different time intervals throughout the study, and that study cost $900,000. It was funded partly by the drug company, partly by a nonprofit that supports cancer research benefitting pets and the rest by private donors. Fortunately, other studies are not this expensive.
The screening and early detection study that was also recently completed was made possible by the support of a breed association and 600 individual donors with contributions ranging from $20 to $10,000.
I personally have made it my life’s mission to help other pet owners facing a diagnosis of this dreadful disease. I created the TCC in Dogs and Cats web site to provide relevant information to help people make informed decisions along with their veterinarians. No matter how you look at it, this cancer is truly heartbreaking. I strongly believe Dr. Knapp has the best chance of finding better treatment options for our beloved pets. I have incorporated Dr. Knapp’s research in my estate plan by creating the Maureen and Tigger Hughes Bladder Cancer Research Fund for Canines at Purdue University. If you want to help Dr. Knapp do more studies for TCC, please use Tigger’s link to support her work. No level of support is too little or too great.
Of course, for those that need Dr. Knapp’s help with their own TCC pet and can travel to Purdue in West Lafayette, IN, here is the link to make an appointment to receive extraordinary care for your TCC pet.
I thoroughly enjoyed my conversation with Dr. Knapp. She is clearly passionate about making a difference in the lives of pets diagnosed with TCC. Her parting words to me were, “We are working on all 3 fronts to combat TCC, but there is still so much to learn. We are learning more every day.”