Sharks and Cancer

 



There is a persistent myth that sharks do not get cancer. Sharks are not immune to cancer but may possess mechanisms that lower their cancer risk. Documented instances of shark tumors have been reported in various species, such as nurse sharks, spiny dogfish, and hammerheads. However, the incidence of cancer in sharks may be lower than in many other vertebrates.

 

Reasons:

One hypothesis suggested is that shark cartilage contains anti-cancer properties because it lacks blood vessels. The idea is that angiogenesis (blood vessel formation) is crucial for tumor growth, and compounds in shark cartilage  inhibit this process. This led to the commercial production of shark cartilage supplements marketed as cancer treatments. 

 

Evidence: Scant

Studies have found little to no evidence that shark cartilage is effective in preventing cancer in sharks or in treating human cancer.

 

Hypothesis 2: 

The genetic makeup of sharks enables enhanced repair mechanisms.

 

Evidence: Seems promising. 

Genome sequencing of sharks, particularly the Great White Shark and the Whale Shark, has revealed genes linked to enhanced DNA repair and stability. Shark immunity genes, such as legumain and Bag1, are associated with rapid wound healing and possibly enhanced resistance to cancer.

 

Hypothesis 3:

Unique aspects of their immune systems provide enhanced cancer-fighting cells.

 

Evidence: It seems promising, but the evidence is slim so far.

Sharks have unique antibodies, IgNAR. IgNAR stands for Immunoglobulin New Antigen Receptor. Unlike conventional antibodies, IgNAR lacks light chains and has an extended complementarity-determining region (CDR3), which enhances its ability to bind diverse antigens. This may allow enhanced attachment to cancerous cells.

 

 

Hypothesis 4: 

Their slow metabolism and unique liver functions (rich in squalene and antioxidants) may help detoxify harmful substances before they can cause cancerous changes.

 

Evidence: Promising.

Shark liver oil is rich in alkylglycerols (AKGs) and n-3 polyunsaturated fatty acids (PUFAs), compounds that have demonstrated antitumor and anti-cachectic effects in experimental models. These substances may inhibit tumor growth and counteract cancer-related wasting.

 

Insight might be gained by studying elephants, another species that has been studied more in terms of cancer prevalence.

 

Elephants and cancer:

Elephants have remarkably low cancer rates despite their large body size and long lifespans. The basic idea is that larger animals, with more cells undergoing division, should have a higher risk of developing cancer. This notion is supported by the observation that, within the same species, cancer risk increases with body size. 

 

However, what if they don’t? This phenomenon is known as Peto’s Paradox. 

That is, Peto's paradox is the observation that the incidence of cancer does not appear to correlate with the number of cells in an organism.

 

Elephants illustrate this paradox by surprising us with their low cancer rates. Researchers have discovered several biological mechanisms contributing to their cancer resistance, especially their DNA repair and tumor-suppressing genes.

 

Reason 1:

The TP53 gene is a crucial tumor suppressor gene that detects DNA damage and either repair it or triggers cell death (apoptosis) if the damage is too severe. Humans have only one copy of TP53, whereas elephants have at least 20 copies (with multiple additional "pseudogenes" that may also be functional). Extra TP53 genes allow elephants to detect and eliminate damaged cells much more efficiently than humans, reducing cancer development.

 

Reason 2:

elephants an extra layer of defense against cancerous mutations.

Elephants possess an ancient, reactivated gene called LIF6 (leukemia inhibitory factor 6). This gene is sometimes referred to as a zombie gene because it was once inactive but evolved to regain function. LIF6 is triggered by TP53 and acts as an additional safeguard against cancer by causing rapid cell death (apoptosis) in damaged cells. This unique feature gives

 

Reason 3:

Elephant cells repair DNA damage more effectively than human cells, preventing the accumulation of mutations that could lead to cancer.

 

Do sharks have more copies of the TP53 gene?

Why yes, they do. Studies on the Elephant Shark and Greenland Shark reveal an expanded TP53 gene family, with multiple copies or insertions within the gene, compared to humans and other vertebrates. These modifications enhance their ability to repair damaged DNA, maintain genome stability, and prevent uncontrolled cell growth.

 

The late-breaking (2025) news/study summarizes what is known about 263 species. Researchers found that larger species do, in fact, have higher cancer prevalence, both for benign tumors (neoplasia) and malignant ones. However, some evolve mechanisms to offset this risk, especially those that grow large quickly.

 

 

Sources and Further Readings:

 

Abegglen LM, Caulin AF, Chan A, Lee K, Robinson R, Campbell MS, Kiso W, Schmitt DL, Waddell PJ, Bhaskara S, Jensen ST, Maley CC, & Schiffman JD. 2015. Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans. JAMA, 314(17): 1850–1860. 

 

American Association for Cancer Research. 2024. Why elephants don't get cancer but ferrets do: Cancer prevalence across vertebrate animals. AACR Blog. https://www.aacr.org/blog/2024/11/06/why-elephants-dont-get-cancer-but-ferrets-do-cancer-prevalence-across-vertebrate-animals.

 

Butler, G., Baker, J., Amend, S. R., Pienta, K. J., & Venditti, C. (2025). No evidence for Peto’s paradox in terrestrial vertebrates. Proceedings of the National Academy of Sciences, 122(9), e2422861122. 

 

Iagher F, de Brito Belo SR, Souza WM, Nunes JR, Naliwaiko K, Sassaki GL, Bonatto SJ, de Oliveira HH, Brito GA, de Lima C, Kryczyk M, de Souza CF, Steffani JA, Nunes EA, Fernandes LC. 2013. Antitumor and anti-cachectic effects of shark liver oil and fish oil: comparison between independent or associative chronic supplementation in Walker 256 tumor-bearing rats. Lipids Health Disease 12: 146. 

 

Lane DP, Madhumalar A, Lee AP, Tay BH, Verma C, Brenner S, Venkatesh B. Conservation of all three p53 family members and Mdm2 and Mdm4 in the cartilaginous fish. Cell Cycle. 2011 Dec 15;10(24):4272-9. doi: 10.4161/cc.10.24.18567. Epub 2011 Dec 15. 

 

Miller DR, Anderson GT, Stark JJ, Granick JL, and Richardson, D. 1998. Phase I/II trial of the safety and efficacy of shark cartilage in the treatment of advanced cancer. Journal of Clinical Oncology 16(11): 3649-3655. 

 

Monash University, 2023. Sharks’ cancer secret also puts them at risk: Study. Available at: https://www.monash.edu/news/articles/sharks-cancer-secret-also-puts-them-at-risk-study

 

National Institutes of Health. 2015. How elephants defend against cancer. NIH Research Matters. https://www.nih.gov/news-events/nih-research-matters/how-elephants-defend-against-cancer.

 

Ostrander, G.K., Cheng, K.C., Wolf, J.C. and Wolfe, M.J., 2004. 'Shark cartilage, cancer and the growing threat of pseudoscience'. Cancer Research 64(23): 8485-8491. 

 

Sahm A, Cherkasov A, Liu H, Voronov D, Siniuk K,  Schwarz R,  Ohlenschläger, O, Förste S,  Bens M, Groth M, Görlich I,  Paturej S,  Klages S,  Braendl B, Olsen J,  Bushnell P,  Bech PA, Ferrando S, Garibaldi F, & Hoffmann S. 2024. The Greenland shark (Somniosus microcephalus) genome provides insights into extreme longevity. 

 

Science Magazine. 2018. Elephants rarely get cancer thanks to a 'zombie' gene. Science. https://www.science.org/content/article/elephants-rarely-get-cancer-thanks-zombie-gene.

 

University of Oxford. 2022. Elephant genes could hold the key to avoiding cancers. University of Oxford News. https://www.ox.ac.uk/news/2022-07-15-elephant-genes-could-hold-key-avoiding-cancers

 

University of Wisconsin–Madison, 2024. 'Fighting metastatic cancer with the help of sharks'. Available at: https://www.uwhealth.org/news/fighting-metastatic-cancer-with-the-help-of-sharks

 


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