General Comments / Chat, page-6089

I wouldn't be surprised if you are correct @johndprent in wondering whether pretreatment FTO status is irrelevant (and by that I suspect you mean whether FTO is up-regulated or down-regulated before determining whether targeting FTO is appropriate)

I realise you're talking about the effect of radiotherapy treatment on the levels of FTO (that the treatment itself elevates FTO), but on a similar theme....

Much of the conversation has been around targeting indications that demonstrate up-regulated FTO; that's where the 15% figure for addressable market for cancer indications comes from.

I've wondered for some time whether there's the potential for Zantrene's usefulness to be higher than the oft-repeated 15% of cancers.

Much higher.

This my lay-person thinking on FTO understanding and why the over-expression theory has developed:

1. The understanding of m⁶A and FTO is still in it's relative infancy and generated lots of excitement and therefore research
2. Studies on m⁶A and FTO led to this paper in 2017 https://www.sciencedirect.com/science/article/pii/S1535610816305608 which acknowledged that FTO is upregulated in AML and further stated that 'FTO Plays an Oncogenic Role in Acute Myeloid Leukemia'
3. If nothing else, that gave us FTO as a potential target for further studies.
4. Thankfully Chen took that lead and did indeed target FTO.
5. In 2020 this paper https://www.sciencedirect.com/science/article/pii/S1535610820302166 Chen demonstrated that ' Targeting FTO Suppresses Cancer Stem Cell Maintenance and Immune Evasion'.
6. He did it using Zantrene (nice surprise, many thanks)
7. Great for the FTO field of research, great for shareholders of Race

So if proving a theory was necessary then it'd seem logical to target indications where FTO seems to be a particularly strong characteristic - i.e. indications where FTO is overexpressed.

Yet it's been proven that pre-treatment levels of FTO is not a fundamental qualifier for inhibiting FTO as a means to improve therapeutic outcomes as a result of inhibiting FTO.


I posed that question to Dr T:



and got this response....





So surely the '15% of cancers where FTO is upregulated' qualification is potentially ....a little too narrow. Deep breath.

To me, the question is possibly much simpler; 'does inhibiting FTO (regardless of the pre-treatment FTO up/down-regulation status) improve therapeutic outcomes?'

There's no reason in my mind why that question shouldn't apply to any indication/treatment 'where FTO is thought to play a role' (radiotherapy included).

This is why, @johndprent, I think you're absolutely right to be curious/intrigued about the graph that @Boffin99 posted.