Yanelys Medina

Advancements in Dog Cancers

Cancer is a crucial issue that affects millions everyday, whether that individual has two or

four legs. For this sole purpose, the rush to find a cure is overwhelming for researchers who are

experimenting everyday. New improvements in treatment for cancer are under constant

development. Therefore, researchers have found alternatives for surgical removal, chemotherapy,

and radiotherapy that could be possible and effective treatments for cancer (Maekawa et al.,

2017). Specifically treating these three cancers; Mammary gland carcinoma, oral malignant

melanoma, and undifferentiated sarcoma. Mammary gland carcinoma is a growth within a breast

(petMD, 2017). This cancer is most common in unspayed female dogs (Case et al., 2017). Oral

malignant melanoma is a disease that damages the tissue and forms small masses in a distinct

area of the mouth (Collins, 2017). For dogs, oral malignant melanoma can even occur in the eyes

(Maekawa et al., 2017). Undifferentiated sarcoma occurs when a tumor forms in soft tissue

(Pisters, Weiss, Maki, & Raut, 2016). Even though the variety of cancer is limited, smaller

improvements can lead to larger ones. I intended to use this topic because I want to become a

veterinarian and I’m sure I’ll come across this issue in the future. What I hope to achieve for my

future patients is to catch their cancer early on and inform their owners about as many effective

treatments that are available for their animal. I believe new advancements towards cancer,

particularly concerning animals will be proven to be beneficial to humans as well.

The most critical part about treating cancer is identifying it early. Prognostic markers are

one way of doing that. Prognostic markers use biological characteristics to, “ predict the course
of a disease” (Nature, 2017, para. 1). Case et al. (2017) explained how there are two main

complications refraining mammary gland carcinoma patients of promising outcomes. The first is

the prediction of dogs at risk for the development and recurrence of this cancer. The second are

effective treatments for these patients. Case et al. (2017) experimented with collagen and its

ability as a prognostic biomarker to stages I, II, and III grade mammary gland malignancies.

“Canine mammary gland carcinoma biopsy samples were obtained [...] to determine the

association between collagen patterns and outcome” (Case et al., 2017, para.7). Thirty-four

biopsy samples were acquired, but only twenty-nine samples were utilized (Case et al., 2017).

Prior to surgery, all of the dogs involved had their tumors measured, complete blood counts,

evaluated lymph nodes, serum chemistry profiles, and thoracic radiographs (Case et al., 2017).

By measuring and evaluating biological characteristics, collagen can determine the course of this

disease (Case et al., 2017). The researchers took into account how many collagen fiber

characteristics affect the efficiency of the prognostic marker. The many variables they accounted

for were the collagen’s density, organization, fiber width, length, and straightness (Case et al.,

2017). They studied these characteristics and compared them with patient survival times.

During this study, they also came across the idea that collagen also allowed the tumors to

regress and discontinue growing. The organization and stiffness of the collagen are essential in

mediating tumor development and metastasis (Case et al., 2017). It “supports the ability of

collagen to play both tumor-permissive and tumor-restrictive roles” (Case et al., 2017, para.27).

This way collagen signatures have proven themselves to be a possible treatment, as it regulates

tumor progression.
 In the second experiment, Grosenbaugh et al. (2011) demonstrates how a safe and

effective vaccine for oral malignant melanoma in dogs has evolved. This vaccine contains

plasmid DNA containing human tyrosinase (Grosenbaugh et al., 2011). Fifty-eight dogs who

were participating in this trial were injected transdermally with four injections of the human

tyrosinase vaccine (Grosenbaugh et al., 2011). There were 111 dogs with varying stages I, II, and

III of their cancers involved in this experiment. Fifty-three dogs were historical controls; a

controlled group of patients whose information is available through past records and used to

compare with new data (Statistics How To, 2017). Every six months, the remaining surviving

dogs were given booster injections. The survival time for the dogs vaccinated with that of the

controlled group were compared. The survival time of the dogs who received the human

tyrosinase vaccine was significantly improved to those of the controlled group, who did not have

the vaccine. Grosenbaugh et al. (2011) states that less than fifty percent of those vaccinated died

of the cancer before the end of the trial. This proves to be a successful treatment because there

were no significant reactions to the vaccine besides mild pain at injection site and acute

post-vaccination bruising (Grosenbaugh et al., 2011).

The research done by Maekawa et al. (2017) introduces the new realm of treatment of

immunotherapy. Immunotherapy takes advantage of the immune system and uses it to fight

diseases (Maekawa et al., 2017). Researchers developed a new antibody that targets and

suppresses oral malignant melanoma, undifferentiated sarcoma, and any other PD-L1 positive

cancers. PD-1 is demonstrated mostly on activated T cells (Maekawa et al., 2017). This

anti-PD-L1 antibody blocks PD-1 (programmed cell death) and PD-L1 (PD-ligand) binding

(Maekawa et al., 2017). This has proven to be effective in inducing anti-tumor immune
responses. To create this antibody, researchers replaced a large part of the antibody with that of a

rats. This was done to avoid rejection upon administration and function appropriately with the

anatomy of a dog (Maekawa et al., 2017). In this study, seven dogs with oral malignant

melanoma and two dogs with undifferentiated sarcoma were administered with the antibody

every two weeks (Maekawa et al., 2017). This treatment proves itself to be effective because just

after ten weeks, two dogs showed a substantial decrease in tumor regression and none of the trial

participants had an allergic reaction.

All three of these experiments had very promising results, and have proven themselves to

be safe and effective treatments for the cancers studied. The experiments had relatively well

forms of controlled variables. The study done by Grosenbaugh et al. (2011) had a large variety of

dogs, which was helpful to see how the vaccine would affect different breeds of dogs. But they

did not specify whether they studied any specific age group, which could be a factor in how the

vaccine and disease affected them. The research done by Case et al. (2017) consisted of a small

trial of dogs. Out of their thirty-four biopsies accounted for, five of them proved themselves to be

unuseful. They stated that they used canine mammary tumor biopsies, which did not identify

clearly the breeds, age groups, and genders of the participants involved. If they had more control

over their variables, the lost data could have never occurred.

The experiment done by Maekawa et al. (2017) had an extremely small clinical study

with only nine dogs in their trial. It could have been more accurate if they included a larger

variety of dogs of different breeds, which they did acknowledge in their discussion. Although, all

three studies did explain how they tested on the different stages (I, II, III) of the cancers. This is

beneficial because it observes how the treatment affected each stage of the cancers studied. The
experiments did have a few flaws, but overall they were very well organized and thought out.

The favorable results overcome the flaws as the outcomes are positive. After analyzing the

results of these three studies, it can be concluded that collagen is a promising prognostic

biomarker at determining mammary gland carcinoma and can even be a possible treatment. Also

the plasmid DNA human tyrosinase and the anti-PD-L1 antibody are effective treatments

towards oral malignant melanoma and undifferentiated sarcoma.

The knowledge and use of all of these treatments can open new doors for more research

to advance the variety of cancers that can be treated and possibly even find a cure for.

Introducing collagen as a prognostic biomarker can help my future cancer patients by informing

their owner’s early on, so early and aggressive intervention can take place. This can prolong the

survival time of my patients and even help save their lives. New technology can allow

researchers to create new antibodies that use different animal characteristics to assure that the

subjects do not have an allergic reaction (Maekawa et al., 2017). Along with plasmid DNA

vaccinations and human tyrosinase which proves that we are advancing into finding a cure for

cancer in dogs and even possibly humans (American Journal of Veterinary Research, 2017). In

my future career as a veterinarian, I plan to share my knowledge with my patient’s owners in

order for their animal to have the best chance of surviving and living their life to its greater

extent. My research has expanded my horizons and opened my mind to other possible treatments

besides just surgical removal. I will support the use of these treatments as they do not have to put

animals through a long healing process like a surgical procedure would. This might affect their

survival time because they could already be weak from the effects of the cancer itself. These new

treatments would only cause bruising and mild pain at the injection site. I believe this research
will persuade me to keep myself updated and further my knowledge of future advancements that

might prove themselves to be beneficial to my patients.

 References

Cancer. (2017). Cancer immunotherapy. Retrieved from

https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunothe

rapy.html

Case A., Brisson B., Durham A., Rosen S., Monslow J., Buza E., … Volk, S. (2017).

Identification of prognostic collagen signatures and potential therapeutic stromal targets

in canine mammary gland carcinoma. ​Plos One​, 12(17), 1-19.

doi: 10.1371/journal.pone.0180448

Collins, B. (2017, March 7). Oral malignant melanoma. Retrieved from

https://emedicine.medscape.com/article/1078833-overview

Grosenbaugh, D., Leard A., Bergman P., Klein M., Meleo K., Susaneck S., … Hess, P. (2017).

Safety and efficacy of a xenogeneic dna vaccine encoding for human tyrosinase as

adjunctive treatment for oral malignant melanoma in dogs following surgical excision of

the primary Tumor. ​American Journal of Veterinary Research, ​72(12), 1631-1638.

doi: 10.2460/ajvr.72.12.1631

Statistic How To. (2017). HIstorical controls. Retrieved from

http://www.statisticshowto.com/historical-controls/

Maekawa, N., Konnai, S., Takagi, S., Kagawa, Y., Okagawa, T., Nishimori, A., … Ohashi, K.

(2017). A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy

in oral malignant melanoma or undifferentiated sarcoma. ​Scientific Reports, ​7(1), 1-12.

doi: 10.1038/s41598-017-09444-2
Nature. (2017). Prognostic markers. Retrieved from

https://www.nature.com/subjects/prognostic-markers

petMD. (2017). Mammary gland tumor in dogs Retrieved from

https://www.petmd.com/dog/conditions/cancer/c_dg_mammary_gland_tumor

Pisters, P. Weiss, M. Maki, R. Raut, C. (2016, June 2). Soft-tissue sarcomas. Retrieved from

http://www.cancernetwork.com/cancer-management/soft-tissue-sarcomas