Anticancer Inspiration from Animal Giants

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.

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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.

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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.

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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.

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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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