Good news! Cancer is history (soon)!
"... As an organism grows older, and its cells continue to replicate, the chances of cancerous mutations increase. And the bigger the organism, the more cells it has, so the more chances for mutations, and the higher risk for cancer as it ages. ...
But this hasn’t been found to be the case, and the discordancy is known as “Peto’s Paradox” after epidemiologist Richard Peto, who discovered per-cell carcinogenesis rates were not consistent between species. In fact, in some larger species such as whales and elephants there seemed to be very little evidence of cancer at all, despite being massive and living long lives. ...
But this hasn’t been found to be the case, and the discordancy is known as “Peto’s Paradox” after epidemiologist Richard Peto, who discovered per-cell carcinogenesis rates were not consistent between species. In fact, in some larger species such as whales and elephants there seemed to be very little evidence of cancer at all, despite being massive and living long lives. ...
A landmark study [in 2016] homed in on one of the key ways these massive mammals may be avoiding cancer. Elephants seem to have 20 different copies of a tumor-suppressing gene known as [tp53]. This gene encodes a protein ... p53, which serves as a crucial cell protector. ...
When the p53 gene is not working properly damaged cells can multiply and cancerous tissue accumulates. Dysregulation of the gene is thought to play a role in more than half of all human cancers, but unlike elephants, [humans] only have one copy of the gene. ..."
When the p53 gene is not working properly damaged cells can multiply and cancerous tissue accumulates. Dysregulation of the gene is thought to play a role in more than half of all human cancers, but unlike elephants, [humans] only have one copy of the gene. ..."
From the abstract:
"The p53 tumor suppressor is a transcription factor with roles in cell development, apoptosis, oncogenesis, aging, and homeostasis in response to stresses and infections. p53 is tightly regulated by the MDM2 E3 ubiquitin ligase. The p53–MDM2 pathway has coevolved, with MDM2 remaining largely conserved, whereas the TP53 gene morphed into various isoforms. ... Elephants such as Loxodonta africana constitute ideal models to investigate this coevolution as they are large and long-living as well as having 20 copies of TP53 isoformic sequences expressing a variety of BOX-I MDM2-binding motifs. Collectively, these isoforms would enhance sensitivity to cellular stresses, such as DNA damage, presumably accounting for strong cancer defenses and other adaptations favoring healthy aging. Here we investigate the molecular evolution of the p53–MDM2 system by combining in silico modeling and in vitro assays to explore structural and functional aspects of p53 isoforms retaining the MDM2 interaction, whereas forming distinct pools of cell signaling. The methodology used demonstrates, for the first time that in silico docking simulations can be used to explore functional aspects of elephant p53 isoforms. Our observations elucidate structural and mechanistic aspects of p53 regulation, facilitate understanding of complex cell signaling, and suggest testable hypotheses of p53 evolution referencing Peto’s Paradox."
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