Pillar 1 - FTO (new thread), page-825

Nothing conclusive as yet. I think I mentioned before that viral replication seems to favor high m6A, but there needs more research before a definitive conclusion can be made. The issue is (and in some ways this is also where the excitement is) that research into the epigenetic mechanism of cancer dominates and so we have a lot of information coming out. The table below highlights that with a number of studies coming out in January relating to cancer and FTO, whereas I couldn't find anywhere near as many for FTO or m6A modification in other areas. Cancer is also specifically looking at FTO inhibitors. This highlights that there is not enough research out there at the moment to make a definitive, conclusive statement about the role of FTO or m6A modification in all disease types.

@Jdmoney is right. Low dose (~7.5 mg/m2) Bisantrene is theorised to inhibit FTO quite well in humans. For the time Bisantrene is in the system, it should have that effect. You raise a really good point about steroids used for other conditions and long-term benefits outweighing risks, which is exactly what I believe the mindset will be for oncologists who use decide to use an anti-cancer agent for an individual.

From what I have read, Bisantrene comes with its toxicities like all other cancer therapies. I am yet to see things that would indicate that FTO inhibition was causing that effect, but I'll keep that in mind when I look next time. One interesting 'side-effect' I have seen routinely in the historic literature is the reduced cardiac risk, which is commonly elevated in anthracycline treatments. Evidence is starting to accumulate about the role of FTO in heart failure (1) and so, this may serve as more circumstantial evidence supporting the role of Bisantrene as an FTO inhibitor, as well as maybe a beneficial cardiovascular agent. More data is needed before definitive conclusions can be made - like a preclinical heart safety model, for example.



1 https://www.frontiersin.org/articles/10.3389/fcvm.2021.647806/full