Peto's Paradox: evolution's prescription for cancer prevention

Abstract

The evolution of multicellularity required the suppression of cancer. If every cell has some chance of becoming cancerous, large, long-lived organisms should have an increased risk of developing cancer compared to small, short-lived organisms. The lack of correlation between body size and cancer risk is known as Peto's Paradox. Animals with 1,000 times more cells than humans do not exhibit an increased cancer risk, suggesting that natural mechanisms can suppress cancer 1,000 times more effectively than is done in human cells. Because cancer has proven difficult to cure, attention has turned to cancer prevention. In this review, like pharmaceutical companies mining natural products, we seek to understand how evolution has suppressed cancer to ultimately develop improved cancer prevention in humans.

Links between metabolism and cancer

“…It stands to reason, then, that the occurrence of cancer in large animals should be much higher in elephants and whales. Known as Peto's paradox, it has been observed that whales have been rarely found to have cancers (Nagy et al 2007;Caulin and Maley 2011). Likewise, the veterinary literature notes that elephants also rarely have cancers, but that feral mice, with several orders of magnitude smaller body sizes, are estimated to have a lifetime frequency of cancer of 40%.…”

The Hdac Inhibitor Sodium Phenylbutyrate Enhances the Cytotoxicity Induced by 5-Fluorouracil, Oxaliplatin, and Irinotecan in Colorectal Cancer Cell Lines

“…Resistance to anticancer therapy can occur through different mechanisms such as impaired permeability, DNA mutations, metabolic changes, DNA damage repair, epigenetic alterations, and others [15]. Epigenetic mechanisms are critical for the normal genetic development of the mammalian cells, and cancer is believed to develop due to the accumulation of genetic and epigenetic aberrations through a multistep process [14][15][16][17][18][19][20][21][22][23], creating a heterogeneous disease at both cellular and molecular levels [24].…”

Peto's paradox and human cancers

“…Peto's paradox is the lack of such a relationship [1] and is good evidence that over the millions of generations of multicellular evolution, natural selection has provided species with levels of cancer protection that are proportional to their body masses and lifespans [2][3][4][5]. Several articles in this Special Issue present background and new results on some of the causes, protection mechanisms and emergent patterns.…”