In reviewing the section on TP53 from Astrocytoma Options, I noted "autophagy inhibition with chloroquine prevented restoration to normal P53 function" and therefore best to avoid autophagy inhibitors. Would someone kindly clarify whether this suggests chloroquine should be avoided for my husband who was found to have TP53 Variants including insertions/deletions?
We have been using it for its purported benefit for EGFR amplification.
If so, are there other autophagy inhibitors to avoid?
Would Zinc be worth adding? (Tried it briefly in the past and experienced GI upset).
Many thanks and healing wishes to all--
This isn't even an issue unless you're attempting to restore normal p53 function using zinc. Autophagy was the mechanism for mutant p53 degradation following zinc exposure.
ReplyDeleteThere are two large uncertainties here: whether zinc can actually help restore normal p53 function in humans (not just in vitro or in lab animals), and whether normal chloroquine doses taken by humans can inhibit autophagy effectively enough to interfere with this. I have my doubts on both issues.
I would not stop using chloroquine on the basis of this paper, especially if his tumor is EGFR amplified.
Do you know which specific TP53 mutation was found in his tumor (for example, TP53 R273H)? Only a certain type of mutant p53 could be influenced by zinc levels, and if his tumor's TP53 mutation is a different type, none of this would matter in his case.
Sorry for the delay in responding. Did not see this initially and have been consumed with re-irradiation treatment. I reviewed the snapshot analysis report we were provided and there were no further details about the TP53 mutation.
ReplyDeleteI am extremely grateful for your response and as always for this enormously helpful site.