The Mystery of Peto's Paradox
DOI:
https://doi.org/10.58445/rars.258Keywords:
Peto's Paradox, metabolism, hallmarks of cancer, oncogenes, tumor-suppressor genes, apoptosis, somatic mutation, Klieber's Law, reactive oxygen speciesAbstract
The mystery of Peto's paradox has perplexed evolutionary biologists for many years. The epidemiologist Richard Peto observed that while animals with larger bodies have more cells and therefore a higher likelihood of genetic mutation, they do not have a higher incidence of cancer. Identifying how larger animals have evolved to suppress cancer may help to resolve this apparent paradox. One hypothesis suggests that larger animals have evolved stronger cancer prevention systems, such as improved DNA repair mechanisms, increased sensitivity to apoptosis, or stronger defenses against uncontrolled cell division. Understanding how larger animals have evolved to resist cancer may help researchers identify new methods of cancer prevention and treatment in humans and animals. This review provides an overview of Peto's paradox and the development of cancer suppression mechanisms in large-bodied animals. We explore recent developments in understanding how larger animals have evolved to suppress cancer, including results from comparative and genomic studies. We also highlight new methods for fighting cancer that take advantage of the synergy between cancer prevention pathways.
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