Hi, I want to thank those of you that responded to my previous post. For some reason, I can write posts but not respond? Anyway, I am trying to figure out additional repurposed drugs/supplements to have my son take with his "main" treatment. Briefly, he had IDH1+ AA3 (diag. originally 1/11) treated with proton alone fall of 2012 with small recurrence found late 12/17 MRI. Eventual surgery showed GBM that is still IDH1+ (as expected) but hypomutated (GTR with very generous margins--tumor in "unimportant" part of frontal lobe). He is enrolled in a clinical trial (metronomic TMZ/PARP). I wanted to make certain that he can tolerate his "main" drugs and then sequentially add supplements/repurposed meds (with the approval of the study supervisors). He is already taking Keppra, melantonin 20 mg and will likely start Celebrex later this week.
--I was going to add Longvida given data...but it states that it "reduces oxidative stress"...isn't the idea to try to stress the IDH1+ residual tumor?
--I was thinking of having him add chloroquine and/or metformin. However, I have read the inhibiting autophagy (as chloroquine purportedly does) can either promote OR suppress tumor growth? He doesn't have a BRAF mutation (or many at all--at least not yet).
--I have read about dihydrotanshinone, that can reportedly cause endoplasmic reticulum stress and sensitize to TMZ. Is this something to consider?
Are there any supplements that seem particularly useful for IDH1+ patients?
Thank you very much, Marcia
The antioxidant capacity of curcumin is concentration dependent. In some studies low concentrations of curcumin have actually increased the production of hydroxyl radical.
ReplyDeletehttps://www.sciencedirect.com/science/article/pii/037851739090201E
Curcumin is considered to be a highly pleiotropic molecule, meaning it has multiple different sites of activity or mechanisms of action. Dozens upon dozens of animal models show an anti-tumor effect of curcumin, while I haven't seen any studies showing a tumor protective effect. This says to me that one or many of the other mechanisms of curcumin are outweighing any potential protective effect related to antioxidant capacity. Moreover I theorize that curcumin may be more beneficial via effects on immune cells, rather than direct effects on tumor cells (for example through STAT3 inhibition).
Autophagy is generally a survival mechanism in situations such as stress from low oxygen or low nutrient availability. There is the idea that autophagy can be an anti-tumor influence in the early stages of tumor development, but that in later stages it plays more of a tumor protective role.
"It can be tumor-suppressing during the early stages of tumorigenesis (i.e., it is an anti-tumor mechanism), as reduced autophagy is found in tumor cells and may be associated with malignant transformation. In this case, induction of autophagy would seem to be beneficial for cancer prevention. In established tumors, however, autophagy can be tumor-promoting (i.e., it is a pro-tumor mechanism), and cancer cells can use enhanced autophagy to survive under metabolic and therapeutic stress."
https://www.nature.com/articles/emm201215
What was the nature of the evidence you saw for dihyodrotanshinone? In vitro only? Animal model?
For IDH1-mutant tumors especially I like long-chain omega 3 fatty acids (EPA + DHA) from fish oil, though this is based on theory rather than evidence.