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:
- The understanding of m6A and FTO is still in it's relative infancy and generated lots of excitement and therefore research
- 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'
- If nothing else, that gave us FTO as a potential target for further studies.
- Thankfully Chen took that lead and did indeed target FTO.
- 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'.
- He did it using Zantrene (nice surprise, many thanks)
- 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.
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