How the Blind Mole Rat Might Help Cure Cancer
A new study uncovers why blind mole rats live 6 to 7 times as long as other rat species—and how they stay cancer-free.
-- by Elijah Wolfson
Mice and rats typically live to be about 3 or 4 years old. Unfortunately (or fortunately, if you are musophobic), these small rodents typically develop cancerous tumors after only a few years of life. In fact, cancer accounts for 90 percent of most mouse and rat deaths.
However, there is one type of rodent that lives relatively long compared to its cousins: the blind mole rat, commonly found in the Middle East, live to be an incredible 21 years old. For comparison, that would be like a human living to be 650 years old. How do they do it? They don’t get cancer.
A new study published today in the Proceedings of the National Academy of Sciences investigates how the blind mole rat wards off cancer—and how this rodent’s natural adaptations might help humans develop the same skills.
The study found that if unchecked cell growth occurs in the blind mole rat, its cells undergo a process the researchers termed “concerted cell death.” In this process, the blind mole rat cuts off oxygen to all cells affected by potentially cancerous growth, effectively killing the cancer before it can spread.
The Expert Take
"Underground life provides a protected environment, away from predators," said Vera Gorbunova, Professor of Biology and Oncology at University of Rochester, and lead author of this study. "This allows for evolution of long lifespan. Cancer resistance is one of the requirements for long life."
It seems that it is something specific to the blind mole rat's life underground that brings about its resistance to cancer. "Living in a low-oxygen environment may lead to evolution of anticancer defenses by mechanisms we do not yet fully understand," said Gorbunova.
One possibility is this: cancer cells grow at abnormal speeds, causing the host's body to require more oxygen than normal. But because the blind mole rat has developed an overly stingy approach to oxygen use (to make up for a pretty much oxygen-less environment), whenever the rat’s body starts asking for more oxygen than normal, the rat simply says no. Thus, it starves the cancer cells of the oxygen they need to grow, cutting them off before they can harm the body.
"Humans do not have same [anticancer] mechanism," Gorbunova said, "but do have all the required genes." If we can figure out how to activate these pathways, we could benefit greatly. As Gorbunova made clear, the exact mechanism by which this happens is not yet clear—but when researchers can figure it out, it may help direct the future of cancer treatment.
The blind mole rat is one of a few animal species currently being studied for their unique longevity and abilities to ward off cancer. According to Gorbunova, these and other "cancer-proof" rodents are particularly useful to study, because they can be easily compared to other well-studied, cancer-prone rodents. Gorbunova also mentioned whales as a potential useful object of study. "A large whale has 1000 times more cells that a human, meaning it has 1000 times greater risk of developing cancer," Gorbonuva said. The fact that whales rarely get cancer means they must have some internal anticancer mechanism that we humans do not have.
According to the authors of this study, the knowledge of naturally occurring anticancer mechanisms such as those found in rodents and other animals could potentially be applied to treating and preventing cancer in humans.
Interferon-beta is already used as a treatment for multiple sclerosis, an autoimmune disease. This study helps make the case that it could be applied to cancer treatment as well. "If we can learn how to activate similar interferon-mediated death of precancerous cells in human," Gorbunova said, "that may have translational value."
However, such a treatment method is not exactly just around the corner. It could take years, or even decades, before anything applicable comes out of this study.
Source and Method
The study, “Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism,” was published in the PNAS Early Edition on November 5, 2012.
Two species of blind mole rat were used: Spalax judaei and Spalax golani. The blind mole rats were not actually given cancer in order to test their cancer-fighting abilities. Instead, tests were performed on rat fibroblast cells in vitro. The cells were forced to grow and replicate at faster-than-normal speeds, and the researchers tested how they responded to the stimulation.
The scientists found that at a certain point, the cells began to secret the chemical interferon-beta. In response to the interferon-beta, the cells underwent a necrotic concerted cell death. In effect, when stimulated to overgrow, the cells died instead.
In 2009, Gorbunova was part of a group of researchers, this time led by Andrei Seluanov, that looked at another long-lived, subterranean rodent: the African (or “naked”) mole rat. The resulting study, published in PNAS, found that the cells of the naked mole rat here hypersensitive to contact inhibition. In layman’s terms, as soon as there is even a smidge of above-normal cell density in the naked mole rat, it halts all cell growth, effectively preventing any potential cancer.
A 2005 study published in the Journals of Gerontology also sought to discover why the African mole rat lived so long relative to other rats. Among other things, the study found that these rodents rarely, if ever, develop cancer.
Interferon-beta is currently used to treat multiple sclerosis, and has been studied as a treatment option for cancer. For example, a 2001 study published in Cancer Gene Therapy, found that interferon-beta could be an effective therapy for prostate cancer and tumor suppression.