[Wot53]

I do wonder if the drugs being developed for cancer treatment where P53 is mutated have potential to be a low dose preventative regime for Li Fraumeni TP53 cases. Perhaps depends on the nature of the genetic mutation as to which drug would work. Eg COTI-2, P28 peptide.

Also I have seen some research around understanding the mechanism of action for Metformin, but it seems to suggest it is a mTOR inhibitor. If so you would think it only helpful if that pathway is implicated in the tumour genesis. But of course it can be other pathways. Perhaps the future preventative regime will be a bit of a cocktail of blockers and/or activating agents.

I would be interested to understand your thoughts and what you might be thinking in regards to the brief for the research you are exploring.

Wotsy

[Wot53]

If there is not much happening, perhaps a question might be ‘what research should be done’? And then perhaps a research trust can be set up for donations directed at specifically establishing this research and seek donations with a clear use of the funds in mind.

I guess though the big question is what research would be best?

[Wot53]

I have looked at the lfs assoc but it is not clear how the funds are used. I also have found a long time passes before posts are accepted or responded to on their forum, unlike here where you usually get responses.

Do you know of anywhere doing research? Perhaps they might have a grants program or similar I could look into?

Wotsy

[Wot53]

Sadly I don’t know any, which is why I posted the question. I know there has been TP53 research in many places around the world (perhaps the most studied gene in history) but I could not find anywhere donations could be directed to further this research or specific for Li Fraumeni.

So if anyone has any it would be great to hear.

Wotsy

[Wot53]

Yes. Had a look. PGD can screen the embryo to ensure no TP53 mutation.

But are the drugs your take to create extra embryo’s for the IVF process safe if you had a LFS?

Wotsy

[Wot53]

Hi Pan

Thank you for the reply and information.

In my family there was a case of childhood cancer, which in the tumour analysis showed a R280K P53 Mutation in one allele and a deletion of the other. The only other case was Melanoma a couple of generations prior but this had no analysis done.

I appreciate analysis of tumours often show mutations that are only in the tumour, however any mutation in P53 raises the question whether it is linked to LFS.

My investigations have not shown a lot of information about the types of P53 mutations that happen with LFS, other than what I found in the COSMIC and iarc databases. Most published articles do not include very much detail on this, nor do they tend to explain the combinations or if it is always the same type of mutation that is passed through the families, or shows in the various cancers that (unfortunately) can happen.

It was also of interest whether the deletion of one allele and retention of normal wild type for the other allele was common or not, and whether this tended to be less problematic than mutation/wild combinations or not.

For many people I suspect they have not looked at the mutation type level but was hoping some may have and that gathering some data here might shed some light.

Regards
Wotsy

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