RACE ONCOLOGY LTD (ASX:RAC) - Pillar 1 - FTO (new thread), page-34 - HotCopper | ASX Share Prices, Stock Market & Share Trading Forum

Originally posted by Mason14: ↑

This study completed in November 2020 describes how FTO influences both obesity and cancer. While most of us may have a basic understanding of how Bisantrene may be used at low dose to inhibit FTO for cancer, I’m not sure I have seen anything with regards to Obesity – another significant challenge in the obesogenic world in which we live.
This article states that FTO proteins are widely involved in adipogenesis (the growth of adipose tissue – commonly known as fat). It does this by influencing the m⁶A level of hormones that relate to eating or molecules related to adipogenesis.
FTOover-expression limited the m⁶A modification of ghrelin mRNA in cell models and increased ghrelin mRNA and peptide levels concomitantly. Ghrelin is a hormone produced by the enteroendocrine cells of the GI tract and is commonly known as the “hunger hormone”, as it increases food intake. Ghrelin levels are highest before meals when hungry and return to lower levels after mealtimes. If FTO over-expression increases ghrelin mRNA and peptide levels, then it may also lead to increased hunger signals being sent to the brain.
Substantialevidence demonstrates that FTO regulates pre-adipocyte (before it’s a fat cell)differentiation by regulating the exonic splicing of the adipogenic regulatorRUNX1T1 by influencing m⁶A levels around splice sites. Also, FTO influences adipogenesis by regulating mitotic clonal expansion (MCE), a prerequisite for adipocyte differentiation that occurs within 48 h of adipogenic stimulation. Lastly, FTO regulated adipogenesis by dominating cell cycle proteins.

Obesity:

The global weight management market is estimated at USD$262.9B in 2020 and is expected to reach USD $423.2 B by 2027. I can’t find a percentage of which is spent on pharmaceuticals to help with weight loss, but I’m assuming it’s going to be a rough percentage of that. Current weight loss drugs on the market include Orlistat (decreases fat absorption), Lorcaserin (induces satiety), Phentermine-topiramate (decreases appetite and induces satiety), and Saxenda (decreases appetite and induces satiety). While these drugs may be effective, they come with a host of potential side effects and some of them some unpleasant gastro-intestinal symptoms.

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@EddyG brought up the possibility of Bisantrene for weight loss a while ago.

The big question here is, is it causation or correlation between FTO, obesity and cancer?

If you're still in lock down and have time on your hands to read a few articles try looking into the different types of FTO variants. Then look at the genetic tests completed to see where people have more of the FTO genes and how this impacts them. There is then the relationship between FTO and obesity - ie, does certain FTO variants cause the obesity, or does it cause the hunger creating the obesity? Then the relationship between FTO and cancer - ie does the FTO variant increase the chances of cancer, or increase the likelihood of obesity that then increases likelihood of cancer?

My understanding is that Bisantrene is an inhibitor of the FTO protein which will help target and kill cancer cells, however it won't reduce the FTO protein (ie, won't reduce reduce hunger). Happy to be corrected on this though..

Also interesting looking into the impact fasting can have on cancer treatments. I believe this is due to the state it puts the body in prior to treatment stressing the healthy cells to fight and the cancer cells to be more exposed to the treatment. This again can be related back to the FTO (hunger) protein in my opinion.

Here are a few links I have read over in the past and just quickly dug up then (I can't remember what side of the ledger they are all on, but it's good to get a balanced view):

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2906751/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3635949/#:~:text=Background,FTO%20genetic%20predisposition%20is%20unknown.

https://www.oncotarget.com/article/16446/text/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6530042/