How Ancient Whales Fight Off Cancer

In the mammalian world, bowhead whales are unrivaled in lifespan and second only to blue whales in size, yet these whales seemingly evade cancer. A recent study led by researchers at the University of Rochester identified that this cancer resistance comes from a protein called CIRBP that helps repair DNA damage. 

Cancer can develop when genetic errors accumulate in cells over time, but bowhead whales, which have a 200+ year lifespan and many cells, have a paradoxical resistance to these diseases. This resistance may be explained by the cold-inducible RNA-binding protein (CIRBP) that is abundant in their tissues. This protein plays an important role in repairing DNA damage, making it significant in fighting cancer. The researchers found that this protein also improved the repair of genetic damage in fruit flies and human cells. 

Bowhead whale fluke, Shpak (2014). Creative Commons License.

In your body, billions of cells divide daily to replace those dying off. As genes are replicated and one cell divides into two, there is a chance that a cell’s DNA will be damaged. While we have cellular defenses against this damage, occasionally, these mutations can evade detection. A person can accumulate these genetic errors as they age, potentially leading to cancer, where cells grow and divide uncontrollably.

If there is a chance of genetic damage every time cells divide, wouldn’t an animal with many cells be more likely to get cancer than a smaller animal? Surprisingly, no. Larger animals have a lower cancer development rate than expected, which is a phenomenon known as Peto’s paradox. There is no singular explanation for this paradox other than evolution – many large animals evolved independently of each other, so they likely evolved a diverse range of ways to prevent cancer.

Since little was understood about how bowhead whales live so long, the University of Rochester researchers studied the whales’ cancer resistance. When they compared gene sequences in mouse, human, and bowhead whale tissues, the researchers found that the whale cells had lower mutation rates. To validate this finding, the researchers used radiation and cancer-causing chemicals to cause genetic damage, and they found that bowhead whale cells were once again the most resistant to mutations.

Specifically, the bowhead whale cells were especially effective at repairing double-stranded breaks in DNA. Double-stranded breaks describe when DNA breaks completely; errors in “gluing” the DNA back together might turn a cell cancerous. The researchers used a gene-editing technology called CRISPR-Cas9 to break a specific location of a gene present in humans, bowhead whales, and mice. When they analyzed how well the cells repaired the damage, they found that bowhead whale cells were best at accurately repairing the double-stranded breaks.

What factor could help explain this difference? CIRBP. The researchers found that this protein is abundant in bowhead whale tissues and typically undetectable in most other mammals. When CIRBP production was sped up in human cells, the frequency of successful DNA repair also increased. This overexpression also delayed cancerous growth in a soft agar substance. Conversely, when CIRBP production was blocked in bowhead whale cells, their DNA repair became more error-prone.

To test the effects of CIRBP overexpression in a living organism, the researchers activated CIRBP genes in fruit flies. This gave the modified flies a longer lifespan when exposed to damage-inducing radiation, which supports that CIRBP helps protect cells from DNA damage and cancer.

The discovery of CIRBP’s role in cancer resistance shines light on evolution’s many ways to fight cancer. The more we know about these pathways, the more we can develop potential cancer prevention methods or treatments. Currently, there are no therapies that target DNA repair to prevent cancer – it was thought that this would be implausible or impossible. However, CIRBP abundance in bowhead whales illustrates a way that certain animals may decrease mutation frequency, which is known as genetic instability. This discovery unlocks an exciting new possibility: if repair-related proteins like CIRBP could be overexpressed, the underlying genetic instability in people who are predisposed to getting cancer could be treated.

By Amelia DeHoff

References:

Cooper, G. M. (2000a). The Development and Causes of Cancer. In The Cell: A Molecular Approach. 2nd edition. (2nd edition). Sinauer Associates. 

Firsanov, D., Zacher, M., Tian, X., Sformo, T. L., Zhao, Y., Tombline, G., Lu, J. Y., Zheng, Z., Perelli, L., Gurreri, E., Zhang, L., Guo, J., Korotkov, A., Volobaev, V., Biashad, S. A., Zhang, Z., Heid, J., Maslov, A. Y., Sun, S., … Gorbunova, V. (2025). Evidence for improved DNA repair in long-lived bowhead whale. Nature. https://doi.org/10.1038/s41586-025-09694-5 

Shpack, O. (2014). A bowhead whale is tail-slapping in the coastal waters of western Sea of Okhotsk [Photograph]. Wikimedia Commons. https://commons.wikimedia.org/wiki/File:A_bowhead_whale_is_tail-slapping_in_the_coastal_waters_of_western_Sea_of_Okhotsk_by_Olga_Shpak,_Marine_Mammal_Council,_IEE_RAS.jpg

Tollis, M., Boddy, A. M., & Maley, C. C. (2017). Peto’s paradox: How has evolution solved the problem of cancer prevention? BMC Biology, 15(1). https://doi.org/10.1186/s12915-017-0401-7