A phylogenetic review of cancer resistance highlights evolutionary solutions to Peto’s Paradox

Abstract

Cancer is a genetic disease present in all complex multicellular lineages. Finding ways to eliminate it is a goal of a large part of the scientific community and nature itself. Early, scientists realized that the cancer incidence at the species level was not related to the number of cells or lifespan, a phenomenon called Peto's Paradox. The interest in resolving this paradox triggered a growing interest in investigating the natural strategies for cancer suppression hidden in the animal's genomes. Here, we gathered information on the main mechanisms that confer resistance to cancer, currently described for lineages that have representatives with extended longevity and large body sizes. Some mechanisms to reduce or evade cancer are common and shared between lineages, while others are species-specific. The diversity of paths that evolution followed to face the cancer challenge involving coding, regulatory, and structural aspects of genomes is astonishing and much yet lacks discovery. Multidisciplinary studies involving oncology, ecology, and evolutionary biology and focusing on nonmodel species can greatly expand the frontiers of knowledge about cancer resistance in animals and may guide new promising treatments and prevention that might apply to humans.

Kimura’s Theory of Non-Adaptive Radiation and Peto’s Paradox: A Missing Link?

“…Peto’s paradox might contribute some insight into answering those questions. Peto’s paradox is the observation that the evolution of a large body size in vertebrates does not apparently incur higher rates of whole-organism DNA damage, mutation, and genetic diseases such as cancer [ 18 , 19 , 20 , 21 ]. Assuming that every single cell in an organism has the same mutation rate, multi-cellular long-lived organisms should be at a higher risk for DNA damage and its negative (or positive) consequences since more cells—and hence more DNA—provide a larger target for mutations, whereas longer life spans provide more time to experience mutation-causing DNA damage.…”

Walking Through Elephant Cancer Resistance: What it can teach us about elephants, genetics and disease defenses

“…According to scientific findings and Peto's Paradox this is not true between bigger and smaller animals of different species, however it does apply when talking about age. Between the same species, older individuals have a higher risk of presenting cancer than younger ones (Nery, Rennó, Picorelli and Ramos, 2022) (Preston et al, 2023).…”

“…Animals like elephants and whales live longer and are bigger but reproduce less often at an older age. Allowing their bodies to preserve as they do not wear out as much and enhancing protection against cancer as the species evolves (Nery, Rennó, Picorelli and Ramos, 2022). Natural selection would fail if animals got cancer and died before they got a chance to reproduce (Arney, 2020), meaning that bodies must have evolved or tried to evolve a kind of mechanism that combats cancer to an extent that ensures reproduction.…”

“…The multifunctional interleukin-6 class cytokine leukemia inhibitory factor, abbreviated as LIF is a tumor suppressor gene associated with elephant cancer. Elephants have 7-11 extra copies of LIF in their genomes (Nery, Rennó, Picorelli and Ramos, 2022). Most mammals only have one.…”

“…Its body is full of cells that are constantly dividing and reproducing. As there is a bigger chance for mutations to develop logic will guide us to assume that they could be more prone to getting cancer: a disease that is present in all multicellular organisms on earth (Nery, Rennó, Picorelli and Ramos, 2022), and that occurs when there is a genetic mutation that causes cell reproduction to lose control. Surprisingly, scientific research findings have proved the contrary and scientists have shown that elephants only have a 3% chance of getting cancer (Callaway, 2015).…”