A fascinating new study from an international team of researchers found that elephants, one of the largest mammals on earth, oddly have one of the lowest rates of cancer. Moreover, the study found that these extraordinary beasts had particular genetic variations that lower their risk of tumors; the results may aid in developing novel cancer treatments for people.
The likelihood of malignant mutations increases as an organism ages and its cells continue to divide. And as an organism becomes older, its risk of developing cancer increases because it has more cells, which increases the likelihood of mutations. Isn’t that so?
This observation has proven true for various species. Cancer risk has been demonstrated to positively correlate with body size in everyone, from taller people to larger canines. Therefore, more significant, longer-living animals should have higher cancer rates than smaller, more transient ones.
But it has been revealed that this is not the case. The discrepancy is known as “Peto’s Paradox” after epidemiologist Richard Peto observed that per-cell carcinogenesis rates were not constant between species. In fact, despite being enormous and having lengthy lifespans, some larger animals, like whales and elephants, appeared to have minimal signs of cancer.
While it is broadly acknowledged that every animal has acquired special skills for fighting disease, researchers have shown a particular interest in elephants. Despite being much larger than humans, these creatures have lifespans comparable to ours and exhibit few indications of cancer, even when they are very old. Compared to 25% of humans, it has been estimated that only 5% of elephants pass away from cancer.
A major study from a few years ago focused on one of the primary mechanisms these enormous mammals may use to avoid cancer. An elephant’s p53 gene, which suppresses tumors, appears to be present in 20 distinct copies. This gene produces the p53 protein, which plays a critical protective role in cells. When it notices any DNA damage or mutation, this protein functions much like a guard and prevents cells from replicating.
Damaged cells can grow and collect malignant tissue when the p53 gene malfunctions. However, unlike elephants, we only have one copy of the gene, and dysregulation of the gene is thought to be a factor in over 50% of all human cancers. This new study determined precisely how the various p53 genes in elephants inhibit cancer.
Fritz Vollarth, the study co-author from the University of Oxford, explained:
“This detailed and intriguing study demonstrates how much more there is to elephants than impressive size and how important it is that we not only conserve but also study these signature animals in minute detail. After all, their genetics and physiology are all driven by evolutionary history as well as today’s ecology, diet and behavior.”
Another gene called MDM2 encodes a protein that effectively inactivates the p53 protein and controls the activity of p53 in a cell. The p53-MDM2 pathway is essential to how healthy cells function because it allows p53 to check a cell’s health and MDM2 to prevent p53 from causing cell death by signaling that everything is working correctly. According to the latest study, elephants have a wide variety of p53 proteins that can help them overcome MDM2 inactivation.
Since we have just one copy of the p53 gene in humans, it doesn’t take much for MDM2 to take control and enable the growth of cancerous cells. However, in elephants, the p53 protein adopts dozens of alternative molecular structures to resist inactivation by MDM2 and prevent the reproduction of many additional cancer cells.
Robin Fåhraeus, the study co-author, added:
“This is an exciting development for our understanding of how p53 contributes to preventing cancer development. The existence of several p53 isoforms in elephants with different capacities to interact with MDM2 offers an exciting new approach to shed new light on p53’s tumor suppressor activity.”
The new study, published on July 6, 2022, in Molecular Biology and Evolution, offers fascinating insights into the defenses elephants developed against cancer. The study shows how these enormous mammals use several p53 molecules to inhibit the growth of cancerous cells and confirms that elephants have more strategies to prevent cancer than smaller organisms.
These findings are expected to have clinical applications for humans in addition to these scholarly insights. Researchers are now provided with several new avenues for targeted cancer therapy in people by emphasizing dozens of distinct ways p53 molecules can be activated.
