Elephant Cancer Resistance: Getting the wrong message from research

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Blogio
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Elephant Cancer Resistance: Getting the wrong message from research

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Post by Blogio » Wed Apr 29, 2020 1:01 pm

There's a relatively new story that elephants don't get cancer. It's difficult to believe we have sufficient expertise in elephant cancer in wild elephants to conclude this. Perhaps the data is better for elephants living in captivity. However, in humans it's more likely that you die with cancer than die from cancer, which is probably true for elephants as well.

Elephants have 10x the number of copies of the p53 DNA damage detecting gene as humans. This supposedly justifies reports that elephants are extremely resistant to cancer. However, if the natural lifespan of humans is longer than elephants with our measly two copies of p53, perhaps researchers are getting the wrong message. Having 10x the copy number of a particular gene should indicate that there is no backup plan for p53. This means that elephants are extremely resistant to cancers caused by DNA checkpoint halts during mitosis, but it may also mean that elephants are extremely susceptible to DNA damage, or that more subtle responses to DNA damage are not possible in elephants.

If the "reporters" had actually read the article, they would have known that "elephant cells evolved to be extremely sensitive to genotoxic stress", which is the researchers admitting that elephants are less resistant to the causes of cancer than other animals, but they have a few tricks to prevent death of the organism.

They also discovered that elephants have excess copies of a gene LIF6 (Leukemia Inhibitory Factor 6), which releases AIF (Apoptosis Inducing Factor) and/or Cytochrome C from mitochondrai. Human cancers frequently use the Warburg effect (hyperpolarization of mitochondria) to prevent release of these factors. In other words, human cancer cells are trying desperately to kill themselves, but the execution fails. This is frequently because some mutation in the apoptosis initiation pathway has been mutated or downregulated by a mutation.

The researchers showed that LIF6 expression alone is sufficient for cells to kill themselves. This is a significant weakness in the system. One would prefer a multi-factorial process to initiate apoptosis, as is found in humans. Therefore, putting this knowledge to work on human cancer is unlikely.
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