Notes on Animal Health, April 2025: Who Doesn’t Get Cancer?

Cancer is a disease of uncontrolled cell proliferation. The underlying cause is damaged DNA, referred to as mutations, that allow the cell to elude normal inhibitory mechanisms and divide uncontrollably. Mutations may be caused by inherited diseases, carcinogens, or, most commonly, random mutations arising during DNA replication.

In humans, higher incidences of cancer occur in people who are taller, and similarly,  large dogs are more prone to develop cancer than smaller ones. Cancer is also more common as we age. Both these correlations seem intuitive. The larger the organism the more cells it possesses, and the higher the chance that one of those cells will accumulate enough random mutations to become cancerous. Likewise, as we age, our cells undergo more divisions and we accumulate more mutations, thus the risk of cancer increases. However, this pattern is not consistent across all mammalian species. For example, whales and elephants are very large and have long lives but very low rates of cancer. In addition, some small animals, such as bats and naked mole rats, have relatively long lives but rarely develop cancer. Understanding the mechanisms by which these species protect themselves against cancer may give us new approaches to treating and preventing cancer in humans and companion animals.

Some very large mammals rarely get cancer
The largest living land mammal, elephants have a cancer mortality rate of around 5%, whereas humans exhibit cancer mortality rates between 11–25%. One of the most important cancer resistant pathways utilized by elephants is the tumor suppressor protein, TP53. This protein binds to DNA and if the DNA becomes damaged it either activates other genes to fix the damage, or if it cannot be repaired, TP53 triggers the cell to undergo apoptosis, or programed cell death. By stopping cells with mutated or damaged DNA from dividing, TP53 helps prevent the development of tumors. While humans have only one copy of TP53, African elephants have at least twenty copies. Thus, the genome of the African elephant is highly protected against the accumulation of cancer-causing mutations in their cells.

The TP53 pathway is now well recognized as an important target for cancer therapy, however delivering on its potential to treat or prevent cancer has proven challenging. For example, numerous compounds have been developed to block the interaction of TP53 with its main negative regulator, MDM2. Nevertheless, for reasons not entirely understood, small molecule inhibitors of MDM2 rarely induce a therapeutically significant apoptotic response. Therefore, current research is focusing on therapies that combine activators of apoptotic pathways and inhibitors of anti-apoptotic proteins, such as MDM2. It is hoped that these combination therapies will be more effective than sole therapeutic approaches.

Whales come in all shapes and sizes, but some of the largest have the longest life spans and exhibit a high degree of cancer resistance. With a maximum lifespan of over 200 years, bowhead whales, are the longest living mammal on earth and are highly resistant to cancer. Although not as well studied, at least some of their anti-cancer mechanisms are different from those of the elephant. For example, they do not have duplications of the TP53 gene. Instead, they have greater expression of genes responsible for DNA repair, resulting in a low mutation rate in their genome. Whales do not need additional copies of TP53 because their protective mechanisms work earlier in the disease-causing process.

Some small, long-living mammals don’t get cancer
It isn’t just large species with long life spans that have found a way to beat cancer, numerous small mammals are also highly resistant to the disease. Bats, for example, are one of the most cancer-resistant species found in nature with long lifespans relative to their body size, ranging from seven to 42 years. The only flying mammal, their cancer resistance mechanisms are also unique. For example, in greater mouse-eared bats (Myotis myotis) tumor promoting microRNAs are downregulated, while cancer-resisting microRNAs are upregulated. In addition, although they exhibit extremely high metabolic rates during flight, they exhibit very low rates of mitochondrial damage. This suggests that bats have developed mechanisms for resisting and maintaining low oxidative stress. Oxidative stress, typically associated with high metabolic rates, is one contributor to DNA damage.

The broader roles microRNAs play in cancer are now being explored. MicroRNAs, as their name indicates, are small RNA molecules just ~20–25 nucleotides long, and are not templates for proteins, like messenger RNAs (mRNA). Rather, they act by binding to their target mRNA at complementary sequences resulting in the inhibition of mRNA translation into proteins followed by the degradation of those target mRNAs. While some microRNAs promote tumor growth, others inhibit it. Research is now focusing on the use of  microRNAs for diagnostic, prognostic and therapeutic purposes in numerous types of cancer, including lung, endometrial, and pancreatic.

Rodents are an extremely diverse group of mammals, some of which exhibit a significant resistance to cancer.  For example, the naked mole rat (Heterocephalus glaber) typically has a lifespan of over 20 years with reports of individual rats living close to 40 years. Indigenous to East Africa, where they live in communal colonies in subterranean tunnels, they are remarkably resistant to cancer with only a handful of cases confirmed in thousands of animals monitored for decades in zoos, research laboratories and the wild.

There appears to be several mechanisms that contribute to the cancer resistance of naked mole rats. First, the rate at which random mutations occur in their DNA is unusually low, and when mutations do occur, they have extremely efficient repair mechanisms. Second, their cells exhibit a very high level of contact inhibition. For example, when most normal mammalian cells are grown in tissue culture, they stop dividing when they come in close contact with each other, forming dense monolayers of cells. Under the same conditions cancerous cells continue to divide, forming clumps of cells piled on top of each other. Naked mole rat cells, however, stop proliferating before the monolayer is even formed. This high level of contact inhibition appears to be mediated by a high molecular weight hyaluronic acid (HA) molecule that is significantly larger than HA produced by humans and many other mammals.

Similar to naked mole rats, blind mole rats (Spalax spp.) rarely develop cancer, though some of their cancer-resistance mechanisms are different from their cousins. When cultured in vitro, their cells exhibit a phenomenon termed concerted cell death (CCD). It appears that when naked mole rat cells undergo rapid cell proliferation it triggers a massive release of interferon β (IFNβ), resulting in rapid cell death. Like naked mole rats, blind mole rats also have high levels of high molecular weight HA in their extracellular matrix. However, in the blind mole rat the HA doesn’t mediate early contact inhibition. Instead, it protects the cells from oxidative stress, and, together with another unique extracellular matrix component, heparinase, produces an extracellular environment that is not conducive to tumor growth and metastasis.

Humans and companion animals may not be particularly resistant to cancer, but we are not alone. Wild carnivores, like domesticated dogs and cats, also are at high risk of developing cancer and some of those cancers are very similar to ones found in humans. For example, mammary adenocarcinomas with characteristics similar to human breast cancer have been identified in jaguars and wild dogs. Bears are also cancer prone; brown bears (Ursus arctos) develop mammary cancer and polar bears (Ursus maritimus) develop hepatic carcinomas at relatively high frequencies.

Much of our understanding of cancer has been achieved using animal models such as mice and rats that have been inbred and/or genetically modified. Although these models have provided us with rich insights into the origins of cancer, they also have their limitations. By studying species that have developed mechanisms to resist the development of cancer, new prevention and treatment modalities may emerge. In other words, naked mole rats and bowhead whales could teach us a thing or two.

– Cindy Cole DVM, PhD, DACVCP



First Five
First Five is our curated list of articles, studies, and publications for the month.

Why do giraffes have spots?
The spotted pattern on the giraffe’s (Giraffa spp.) coat help hides vulnerable young calves in the brush, but  a new study suggests that the dark spots may also play an important role in temperature regulation. Each dark spot has an underlying dense network of blood vessels, and because dark fur absorbs more of the sun’s heat than light fur, giraffes with more dark spots may be better able to withstand cold temperatures. However, when temperatures rise, those same animals may be at greater risk of hyperthermia. As global temperatures warm, scientists hypothesize animals with fewer dark spots may be at a thermal advantage.

Finding a babysitter is never easy
Many primates use a cooperative breeding strategy whereby they share responsibilities for looking after infants. It gives mothers a break while also allowing younger and less experienced individuals to gain parenting skills. A new study from China found that mothers preferred babysitters who had more experience to naïve ones. Young and inexperienced females still got their turn to care for the infant, typically after a more experienced monkey finished her initial babysitting duties.

Detection Dog Training Improved
Detection dogs are required to learn and alert to multiple different odors during training and to generalize this learning to similar odors when working. Traditionally, most dogs are trained one scent at a time, presenting one target odor in isolation and adding additional odors consecutively. The results of a recent study, however, revealed that dogs trained by intermixing multiple scents from the initial training were more accurate and sensitive at their detecting than dogs trained by the traditional method. The intermix method is faster and thus less expensive and time consuming than traditional training approaches, which should allow more dogs to be trained without the need for additional resources.

Return of the Tasmanian Devils
Thousands of years ago, Tasmanian devils (Sarcophilus harrisii) lived on the Australian mainland. Then, probably due to the arrival of the dingo (Canis lupus dingo), along with pressure from humans, they disappeared. Dingoes never made it to Tasmania, which was cut off from the mainland around 10,000 years ago by rising sea levels, and so the devils survived there. Recently, there has been an effort to return the devils to the mainland. At first some were brought over as an insurance population, because their numbers in Tasmania were being devastated by devil facial tumor disease, a contagious form of cancer. Now it is hoped that they can help control the fox and feral cat populations, which are booming in Australia, ironically, due to a collapse of the dingo population.

Bird Flu in Cats
The American Veterinary Medical Association (AVMA) recently warned cat owners of the danger avian influenza A (H5N1), also called bird flu, poses to their pets. Since March 2024, when the outbreak was first recognized in dairy cattle, dozens of cats, both domestic and wild, have been infected. Cats can develop severe illness, often resulting in death. It is important to limit the exposure of cats to the virus because currently there is no vaccine to prevent the infection and only supportive care for treatment. Unpasteurized milk and raw or undercooked meat, including retail pet diets that contain raw meat, have been the source of H5N1 infections in both pet cats and captive big cats. In addition to these products, cat owners should limit their pets’ exposure to unpasteurized dairy products, wild birds and poultry, livestock and their environments, where possible. Farm workers should also be aware that their contaminated clothing can be a source of infection. Cat owners should consult their veterinarian if they suspect their pet may be suffering from bird flu. The illness typically presents first as loss of appetite, lethargy, and fever, and can quickly progress to include severe neurological and respiratory symptoms.

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