Release date: 2017-07-25

In recent years, naked mole rats, elephants and bowhead whales have caught the attention of cancer researchers. At first glance, these three animals have almost no resemblance: the naked rodent, the rodent, lives underground; the elephant walks on land; the bow-headed whale swims in the sea, but the three do have similarities. . First, they have a relatively long life span: naked moles can live thirty years old and have a much longer lifespan than most of the same species; some elephants can live for up to seventy years; the average lifespan of bowhead whales It lasted for two centuries.

Second, these three species are basically immune to cancer. People often forget that animals, like us, are also fighting with cancer. In recent years, researchers have realized that studying cancer of different species may yield something, which opens up a new field called comparative oncology. For example, a 2015 review mentioned that dogs are ten times more likely to develop cancer than humans, while nude moles, elephants, and bow-headed whales "seems to be completely immune to cancer."

Researchers believe that complementing this "cancer risk map" can provide valuable new insights into the genetic basis of cancer.

Understanding diseases by animals

The data scientists have obtained from pets have proven that this research method works well. The researchers wrote: "The breeding of dogs inadvertently forms a high-risk breeding mode, and dogs born in this way are more likely to develop the disease-specific diseases." At the same time, genetic variation in many purebred dogs is limited. , reducing the difficulty for researchers to identify cancer-related genes. Moreover, dogs have a short life span and physiological functions are similar to humans. Therefore, to evaluate whether new research methods for cancer prevention and treatment are effective, it is more efficient to use dogs as subjects. Professor Michael Kastan of Duke University specializing in cancer biology told The ASCO Post: "Pets (mainly dogs) suffer from cancer due to aging. In recent years, academics have once again become interested in this type of cancer and human cancer. A lot of commonalities.” A 2013 study concluded that the similarities between canine breast cancer and human breast cancer demonstrate that it is feasible to use dogs as a template to screen certain cancers and identify their biomarkers.

The Zoobiquity, published in 2013, may be a source of inspiration for researchers interested in exploring cancer risk profiles. Its author, Barbara Natterson-Horowitz, is a cardiologist at the University of California, Los Angeles. She believes that researchers should start with a humanoid species through an evolutionary perspective to find ways to treat disease. Natterson-Horowitz believes that it is not wise for veterinarians and doctors to work together and lack cooperation, because animals and humans are plagued by many of the same diseases, especially all types of cancer.

Natterson-Horowitz also wrote in the book: "The jaguar is at risk of breast cancer and may carry the BRCA1 gene. The BRCA1 gene carriers, among many Jews with German bloodlines, are at high risk for breast cancer." It also said that animals will also get other types of cancer. For example, captive rhinoceros will have leukemia, and animals suffering from skin cancer will have a wide variety. Therefore, if doctors, veterinarians, and wildlife experts work together, it may help us to deepen our understanding of these diseases. “Even if we can find a cure.”

For several decades, rapamycin has been used to prevent organ transplant rejection, and the University of Guelph's Ontario Veterinary College is conducting clinical trials to test whether this drug can be used to treat canines and prevent osteosarcoma, the most dangerous bone cancer. diffusion. The researchers hope that these therapies will ultimately help the suffering osteosarcoma patients.

Elephant does not have the secret of cancer

It is equally useful to study why certain species do not develop cancer. Evolutionary biologist Vincent Lynch believes that understanding the epidemiologist Richard Peto's "Peto's Paradox" in 1977 is the key to solving the problem. Because cancer is caused by a deleterious genetic mutation, the more cells there are, the higher the chance of a genetic mutation. It is inferred that large-scale multicellular animals such as elephants have a higher risk of cancer than small-sized multicellular animals with short life spans such as mice, but the opposite is true. For example, the number of cells in an elephant is more than one hundred times that of humans, and its cancer incidence is only 5%. In contrast, the incidence of cancer in humans is as high as 20% to 25% (excluding smoking, etc.) The reason is that people with increased risk of cancer).

To understand this paradox, Lynch and colleagues began to compare the genomes of small animals that are susceptible to cancer, such as elephants and large animals that are not susceptible to cancer, and hyrax (a guinea-like animal). The hoof seems to have nothing to do with the elephant, but it is the closest to the elephant in the existing species. In a study published in eLife in 2016, Lynch and colleagues found that although elephants are large, they have evolved another 19 TP53 genes called "suppressor masters". This may be an elephant that can crack Peto. Part of the reason for public opinion. Researchers believe that this is essential for cancer prevention because the TP53 gene kills specific cells to cope with multiple stimuli such as DNA damage. The hoofed rabbit, which is much smaller than the elephant, has only one TP53 gene (there is only one human).

Lynch speculates that these additional TP53 genes may shorten the time it takes for cells to repair various DNA damage, allowing cells to regenerate before programmed death, thereby reducing the likelihood of genetic mutations. "You can't jump out of the framework of evolution to understand biology," Lynch said. "We are also advancing the application of evolutionary thinking in medicine. Comparative oncology is a subdiscipline. In this field, we must first understand the evolution of each species. To understand physiological processes such as cancer."

Vera Gorbunova, a biologist at the University of Rochester who studies nude and blind moles, agrees. In a study published in Nature in 2013, Gorbunova and co-authors found that a sugar secreted by a naked mole rat cell, hyaluronic acid, might explain why the species is immune to cancer. The hyaluronic acid molecules in nude mice are much larger and more abundant than humans and other mammals. This is obviously because this “slimy” substance can make their skin slack and elastic, and the naked mole that burrows underground for life is very useful. Researchers suspect that high concentrations of hyaluronic acid may have been inhibiting cell division, preventing cell overgrowth, inhibiting the growth and spread of cancer cells, and thus playing a role in cancer resistance. Gorbunova said: "We may be able to develop strategies to find ways to make cancer-prone people secrete more hyaluronic acid."

Applying the elephant's anti-cancer mechanism to the human body seems to have dawned. Researchers have begun to inject more TP53 from elephants into human cells. Lisa Abegglen is a geneticist and supporter of evolutionary medicine at the University of Utah. In her recent research, she and her colleagues have successfully synthesized many TP53 genes and injected them into human cells. Human cells have accepted the synthetic TP53 gene, and after the researchers triggered DNA damage, human cell death increased, which prevented cancer cells from spreading.

The researchers acknowledge that it will take years to turn these findings into a cure for various cancers, not to mention cancer prevention. But researchers are optimistic that it might be possible to find a way to fight cancer from cancer-fighting animals. Abegglen said: "So far, we understand one thing, that is, all species have evolved a unique mechanism of cancer. Elephant genes can work in human cells, it is incredible, but it is true. so cool!"

Source: Global Science

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