Saturday, 8 April 2017

Chloroquine and non-P53, non-EGFR mutant tumors

I know that chloroquine has been discussed to death in this site and the original message board but I couldn't find an answer to my question there and am hoping someone can provide some insight.

My understanding is that chloroquine generally works best for those with EGRF mutations. My wife does not have this.

It's a bit unclear as I came across another post in another site (that I cannot find again) that seemed to say that chloroquine works better for those with a P53 mutation while other posts, particularly Stephen's comment in this post, noted that it works better for those without a P53 mutation. I note that we also have a PTEN loss as well.

Finally, this post noted that Chloroquine provides a "strong antimutagenic effect" but it's unclear if it's universally so or if it's only for those that with the aforementioned mutations.

Question: If someone has both a non-P53 and a non-EGFR mutant tumor, is it worth adding Chloroquine if we're past radiation and chemotherapy? We are currently on Optune and Nivo along with our cocktail.

Followup Questions: For those on chloroquine, has anyone noticed any side-effects beyond the retinopathy issue?

My wife's pill burden is heavy enough so I have to be judicious in what we add. I am most drawn to Chloquine because it's one pill, seems to have few side effects, and is a small pill at that.


  1. hello Logan,
    my husband takes Chloroquine (plaquenil in my country), for more than 2 years now and his MRI is stable , no tumor. and no side effects.

    1. Thanks for this, Melinda. May I ask what else you do besides the chloroquine?

    2. I read the last post of my husband cocktail and is pretty the same now, except Levitaricetam (keppra) wich is lower dose now, is 500 g x 2 / day the rest you can see here


  2. My answer to the first question would be: maybe.

    The source for the comments about chloroquine and p53 is this study:

    It was a mostly in vitro study, that tested the effects of chloroquine in various cell lines of varying p53 status, at concentrations of 10-40 mcg/mL (micrograms per milliliter). These concentrations translate to 30-125 micromolar.

    Compare those concentrations with the steady-state maximum plasma concentration in four patients taking the standard 155 mg chloroquine base per day: 1-2 micromolar.

    Furthermore, although U87 cells, which were sensitive to chloroquine in this study, have a non-mutant p53 gene, other studies have shown U87 expresses mostly a mutant-type conformation of the p53 protein due to high expression of zinc-binding metallothioneins.

    Many tumors with a genetically normal TP53 gene might actually be expressing mutant-type conformation of the p53 protein due to this phenomenon, so it's not as simple as "wild-type versus mutant".

    There are other proposed indirect mechanisms for chloroquine, such as effects on the vasculature, which would likely be independent of tumor EGFR or p53 status:

    I personally wouldn't place too much importance on the p53 question, the evidence in relation to chloroquine is tentative at best.

    Unfortunately there are more questions than answers as far as who should take chloroquine and when, so my answer has to be "maybe".

    Current trials, such as will hopefully answer some questions in time.

  3. I have asked this very question to a researcher and received the same response as Stephen has provided above - however I was also given the following information:There is also some evidence though that the effects of chloroquine might be autophagy-independent by affecting tumor vascularization..
    and there are some other challenges:

    1. Yes the issue of autophagy inhibition versus autophagy induction, and the important role of autophagy in immune response adds considerable complexity to an already complex problem.

    2. Tone and Stephen, thank you both for the comments. Let me pull up these reports and take a look.

  4. New question: It seems that chloroquine isn't recommended for epileptics, which I find odd as aren't all GBM patients by definition epileptics?

    "Patients with history of epilepsy should be advised about the risk of Chloroquine provoking seizures."