Solving Peto’s Paradox to better understand cancer

Autor: Viviane Callier
Rok vydání: 2019
Předmět:
Zdroj: Proceedings of the National Academy of Sciences. 116:1825-1828
ISSN: 1091-6490
0027-8424
DOI: 10.1073/pnas.1821517116
Popis: Cancer is as ancient as multicellularity itself. But not all animals get cancer at the same rate. Some, such as elephants and naked mole rats, rarely get it at all, whereas others, such as ferrets and dogs, have cancer at unusually high rates. The question is why. Despite their size and lifespan, elephants are able to stave off cancer by having 20 copies of the tumor suppressor gene TP53 and 11 extra copies of LIF. Image credit: Shutterstock.com/ronnybas frimages. In 1977, British epidemiologist Richard Peto reasoned that the cells in large-bodied, long-lived animals undergo more cell divisions, and every cell division carries a small but nonnegligible risk of introducing mutations in the daughter cells. Some of those mutations could lead to cancer. So all else being equal, one would expect that large-bodied, long-lived animals would have a greater risk of cancer than small, short-lived ones. But when Peto looked into cancer incidence in some of these animals, that’s not what he found. This seemingly counterintuitive phenomenon was dubbed Peto’s paradox (1). To unravel the mystery of Peto’s paradox, researchers are studying the genome sequences of animals across the tree of life, especially those that are particularly large or particularly long-lived. But there’s no one answer. Every species studied so far seems to have solved this paradox in a different way, possibly because of different life histories and evolutionary selective pressures. Such work could offer leads for treating or preventing human cancers, says Joshua Schiffman, a pediatric oncologist at the Huntsman Cancer Institute at the University of Utah. His research shows that the set of genes and signaling pathways that are deficient or broken in patients with a high genetic risk of cancer are actually the same ones that are protecting the animals (2). “Now we can say, ‘Nature has …
Databáze: OpenAIRE