Anticancer Inspiration from Animal Giants

Large-bodied animals across the tree of life have evolved unique ways to combat cancer which could inspire novel therapeutic strategies.

Written byHannah Thomasy, PhD

| 4 min read

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Mammal body size varies tremendously, from the Etruscan shrew, which weighs less than two grams, to the blue whale, which can grow to an impressive 200 tons. Yet mammals with millions of times more cells than their tiny relatives aren’t proportionally more likely to develop cancer, even though their lifespans are usually much longer. Researchers are currently studying the genetic and proteomic quirks of these giants from many different mammalian orders, hoping to discover new ways to fight this deadly disease.

A phylogenetic tree showing the evolutionary relationships of different mammalian orders. Four orders are shown in bold (elephants, dugongs & manatees, rodents, and cows, deer, whales & dolphins). From these, a silhouette of one animal giant from the order is shown on the right (an elephant, a manatee, a capybara, and a bowhead whale).

A diagram of an elephant on a yellow background, underneath it is an arrow pointing up to indicate increased copy numbers of the genes TP53 and LIF, which are involved in tumor suppression.

African elephant: The African elephant is one of the most intensively studied large mammals in the context of cancer resistance. Within its genome, scientists have identified multiple copies of the tumor protein 53 (TP53) and leukemia inhibitory factor (LIF) genes, both of which play important roles in tumor suppression, including the initiation of apoptosis in cells with DNA damage.

A diagram of an manatee on an orange background, underneath it is an arrow pointing down to indicate the loss of the genes MLKL and RIPK3, which are involved in necroptosis.

West Indian manatee: A recent preprint found that manatees, along with their relatives the dugongs, hyraxes and elephants, have lost several genes involved in necroptosis and pyroptosis, including mixed lineage kinase domain-like pseudokinase (MLKL) and receptor-interacting protein kinase 3 (RIPK3). Since necroptosis can promote tumor metastasis, researchers proposed that these losses may be protective.

A diagram of a capybara on a teal background, underneath it is an arrow pointing up to indicate expansions of the genes MAGEB5 and GZMB, which are related to T cell-mediated tumor suppression.

Capybara: While the capybara is smaller than many other giants of the animal kingdom, at 65kg, it dwarfs every other rodent species, many of which tip the scales at only a few hundred grams, or even less. The capybara genome contains expansions of gene families melanoma antigen family B5 (MAGEB5), and granzyme B (GZMB), which play important roles in pathways related to T cell-mediated tumor suppression.

A diagram of a whale on a light blue background, underneath it is an arrow pointing up to indicate duplication of the gene CDKN2C, which regulates the cell cycle, and increased CIRBP, which is involved in DNA repair.

Bowhead whale: Bowhead whales may have multiple mechanisms of cancer resistance. In preprints that analyzed the genome and the cells of bowhead whales, researchers identified a retroduplication of the gene cyclin-dependent kinase inhibitor 2C (CDKN2C), which regulates the cell cycle, and elevated levels of cold-inducible RNA-binding protein (CIRBP), which is involved in DNA repair.

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References

Abegglen LM, et al. Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans. JAMA. 2015;314(17):1850-1860.
Vazquez JM, et al. A zombie LIF gene in elephants is upregulated by TP53 to induce apoptosis in response to DNA damage. Cell Rep. 2018;24(7):1765-1776.
Birkemeier M, et al. Pervasive loss of regulated necrotic cell death genes in elephants, hyraxes, and sea cows (Paenungualta). bioRxiv. 2024.04.04.588129.
Herrera-Álvarez S, et al. How to make a rodent giant: Genomic basis and tradeoffs of gigantism in the capybara, the world’s largest rodent. Mol Biol Evol. 2021;38(5):1715-1730.
Vazquez JM, et al. A CDKN2C retroduplication in bowhead whales is associated with the evolution of extremely long lifespans and alerted cell cycle dynamics. bioRxiv. 2022.09.07.506958.
Firsanov D, et al. DNA repair and anti-cancer mechanisms in the long-lived bowhead whale. bioRxiv. 2023.05.07.539748.

Meet the Author

Hannah Thomasy, PhD

Hannah is an Assistant Editor at The Scientist. Her work has appeared in The New York Times, The Daily Beast, and Undark. She earned her PhD in neuroscience from the University of Washington where she studied traumatic brain injury and sleep. She completed the Dalla Lana Fellowship in Global Journalism in 2020. Outside of work, she enjoys running and aspires to be a participant on The Great Canadian Baking Show.

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