Anti-cancer mechanisms in Mammals

Why Are Some Mammals More Resistant to Cancer?

Cancer is a group of diseases characterized by an uncontrolled division of cells leading to the invasion and destruction of surrounding tissues and organs. Another characteristic is their capacity to spread to other organs of the body where they establish a new niche of cancerous cells through a process named metastasis.

Several factors, such as hereditary or acquired mutational inactivation of tumor suppressor genes, contribute to the transformation of normal cells into cancer cells. Interestingly, some animals possess the capacity to resist cancer as they evolved more efficient tumor suppressor mechanisms [1].

Mechanisms of cancer resistance in long-lived mammals

Several species, including the naked mole-rat, the elephant, and the bowhead whale are known to be extremely cancer-resistant [2]. The naked mole-rat (Heterocephalus glaber) is an East African mouse-sized rodent that lives in subterranean tunnels. They are considered to have a lifespan that exceeds by far that of other rodents [3].

This species evolved anti-cancer mechanisms by producing large quantities of high molecular mass hyaluronan (HMM-HA) that promotes the inhibition of fibroblasts’ early contact which triggers cell cycle arrest and prevents hyperplasia.

HMM-HA also acts as an antioxidant, that reduces damages to nucleic acids and proteins that are induced by reactive oxygen species (ROS) [2].

On the other hand, elephants evolved a different anti-cancer mechanism that involves the presence of 19 extra copies of the TP53 gene (pseudogenes) in their genomes. Par comparison, humans have only a copy of this gene. TP53 is a key tumor suppressor gene that induces apoptosis in response to DNA damage and oxidative stress, and therefore, prevents the emergence of cancer cells [4].

Finally, the anti-cancer mechanisms that were evolved in the bowhead whale are still unknown and may involve genes that are involved in cancer and aging such as the excision repair cross-complementation group 1 (ERCC1), which encodes a DNA repair protein and uncoupling protein 1 (UCP1) [5].


Several mammals evolved anti-cancer mechanisms that are not observed in other species. Understanding the molecular mechanisms that evolved in these species and others, will allow the development of cures for humans that could lead to new breakthroughs in cancer therapy and prevention.


[1] Rangarajan, A., Hong, S.J., Gifford, A. and Weinberg, R.A., 2004. Species-and cell type-specific requirements for cellular transformation. Cancer cell6(2), pp.171-183.

[2] Seluanov, A., Gladyshev, V.N., Vijg, J. and Gorbunova, V., 2018. Mechanisms of cancer resistance in long-lived mammals. Nature Reviews Cancer18(7), pp.433-441.

[3] Buffenstein, R. and Jarvis, J.U., 2002. The naked mole rat–a new record for the oldest living rodent. Science of aging knowledge environment: SAGE KE2002(21), pp.pe7-pe7.

[4] Abegglen, L.M., Caulin, A.F., Chan, A., Lee, K., Robinson, R., Campbell, M.S., Kiso, W.K., Schmitt, D.L., Waddell, P.J., Bhaskara, S. and Jensen, S.T., 2015. Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans. Jama314(17), pp.1850-1860.

[5] Keane, M., Semeiks, J., Webb, A.E., Li, Y.I., Quesada, V., Craig, T., Madsen, L.B., van Dam, S., Brawand, D., Marques, P.I. and Michalak, P., 2015. Insights into the evolution of longevity from the bowhead whale genome. Cell reports10(1), pp.112-122.

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