Chloroquine (Malaria Pill) for Eliminating DCIS

Lisa123456

I'm wondering if anybody has enrolled in this clinical trial (in Virginia, with results expected in Sept 2016) ? http://www.ncbi.nlm.nih.gov/pmc/articles/PMC377936...

with clinicaltrials.gov identifier NCT01023477

They'll be testing anti-malaria drug Chloroquine, 250 mg/week vs. 500 mg/week for 4 weeks, possibly combined with vitamin D3. They are expecting to eliminate DCIS in tissue.

I'm considering trying it at home for my LCIS, as it seems pretty straightforward with such an easily-obtainable and cheap drug. I'm thinking, I could have gone to Haiti or a similar place, and would have been prescribed this medication. Millions of people around the world take it in much larger doses for much longer period of time. I'm not on any medications at the moment, so there shouldn't be any problem with interactions. The only issue I see is that even if it helps, I won't know because my surgeon refused to do an excisional biopsy.

aliana0

Didn't those scientists get a patent on the drug (chloroquine) for that use? They must really believe it stops pre-invasive DCIS cells. What I got out of what they wrote is that DCIS cells eat parts of themselves (autophagy) when they don't have enough oxygen or nutrients and that this is how they survive somehow. I read something about how a scientist named Otto Warburg said that cancer cells can thrive on sugar in a low oxygen environment and survive by fermentation, not in the way normal cells survive. When I think of fermentation, I think of the fermentation of sauerkraut or alcoholic drinks. I don't really comprehend what exactly the process is, but it seems some scientists say he was right. I think Otto Warburg said cancer is a metabolic disease caused by damage to the cell's mitochondria. He said many things can cause damage to the cell's mitochondria.

Some people think if you don't eat any sugar, the cancer cells can't survive, but wouldn't they get sugar from any food you ate, not just carbohydrates? I thought that damaged cells destroying themselves is a good thing, but maybe not if they use autophagy and eat parts of themselves and still survive somehow. I don't get how they survive after eating parts of themselves. I also don't get how cancer cells survive on fermentation like yeast. Evidently, the idea of using chloroquine is that chloroquine stops DCIS cells from being able to use autophagy to survive.

About Otto Warburg:

http://www.alkalizeforhealth.net/Library/oxygen2.h...

AN OLD IDEA,
REVIVED: STARVE
CANCER TO DEATH

http://www.nytimes.com/2016/05/15/magazine/warburg...

AACR news: Autophagy-addicted breast cancers killed by anti-malaria drug, chloroquine

http://www.eurekalert.org/pub_releases/2013-04/uoc...

The role for autophagy in cancer

Eileen White

https://www.jci.org/articles/view/73941

ee01

Will the trial last for four weeks just to see if there is any effect on the DCIS or are they expecting it to be cured in 4 weeks? If you try it on your own, will you do it for 4 weeks and then see if there are any changes in your next mammogram? How else would you know if it is working? I like your idea.

Lisa123456

From what I read about the trial, I understand they are expecting to "cure" DCIS in 4 weeks, but they are not sure whether 250 mg/week would be enough or the patients must take 500 mg/week, which, is, actually, a standard dose for malaria prevention.

Regarding how I could check my DIY cancer cure: I'm having a baseline MRI next week, so after that's done, I'll wait for the results of the clinical trial (expected in September) to see what dose to take. Then I'll take the pills and wait for my next MRI. I realize it's not ideal, but I just don't want to wait 10 years for this simple treatment to get approved and become part of the "protocol". If my little experiment won't do any good, at least it shouldn't hurt. Maybe I'll visit Madagascar while I'm at it so I don't waste malaria pills

mountainmama1973

Lisa,

I think I will jump on this too....I have done all kinds of stuff like this since first being diagnosed last OCT. I read a study in Life Extension about Metformin preventing breast CA and started taking that. I take DOZENS of supplements, eat a plant based diet and try to remain calm. I had surgery in March after doing all of this other stuff and the DCIS which was high grade 3, with comedonecrosis and microinvasion in OCT came back Grade 2 in March....So maybe it helps. Anyhow....I saw this study today in one of the Clinical Trial adverts I got and I, too immediately thought: WOW! This could be GREAT. I am going to try to have an MRI done soon....But I live overseas in Manila so not so easy to find a dedicated MRI and someone that can read it....Will keep the group posted though!

Cheers,

M

exbrnxgrl

On a note unrelated to bc, but related to chloroquine, I regularly took it over a two year period in the late 1970's, when I was a Peace Corps Volunteer. I had no side effects, nor do I remember any other volunteers having problems with the drug. Good luck

aliana0

I know that rheumatologists give a form of chloroquine for certain conditions (Plaquenil).

Somehow by eating parts of themselves, the cells "recycle" nutrients and at least some of them stay alive. I am guessing when the abnormal cells start piling on top of each other, they crowd each other out to the point that they can no longer get whatever nutrients they need, so they use autophagy to keep surviving.

I mentioned Otto Warburg because it seems he believed that cancer cells eat glucose non-stop and that relates to the cancer cells getting nutrients. I am guessing that normal cells don't eat sugar non-stop, but get full and stop eating. Somehow cancer cells end up metabolizing glucose to lactic acid-apparently the same lactic acid that causes you to feel the burn or soreness when you exercise. He already understood all of this about cancer cells circa 1930/1931.

Maybe chloroquine can nip the cancer cell growth and survival in the bud. I hope so.

It's good to know that chloroquine may not cause severe side effects.

They also mention Metformin in one of the articles below. I have read that having diabetes or having consistently high insulin levels makes it much more likely that cancer will develop. For some reason, having consistently high insulin is apparently a big risk factor for getting cancer, and being overweight apparently puts women at higher risk of getting cancer, though I know some very slender women who got cancer. I am not thin, at least not anymore, and I wonder if this contributed to me getting DCIS. One of my doctors said the type of diet won't make any difference regarding the DCIS, but also said to lose weight. This, too, I think, relates to what Otto Warburg said about cancer cells and glucose metabolism.

Role of autophagy in breast cancer.

http://www.ncbi.nlm.nih.gov/pubmed/17786023

Role of Autophagy in the Therapeutic Response of Breast Cancer Cells

http://www.bcgsc.ca/project/role-of-autophagy-in-t...

The Role of Autophagy in Cancer: Therapeutic Implications

http://mct.aacrjournals.org/content/10/9/1533

SummerAngel

I've been taking Plaquenil (hydroxychloroquine) for about 4 years. No side effects, but it obviously didn't stop my cancer. It is not exactly the same drug, though.

aliana0

Also, autophagy has two opposite effects:

Breast Cancer and Autophagy, pp. 53-88

Some evidence suggests that autophagy acts as a tumour suppressor and should be stimulated to
decrease the incidence of cancer in breast cells. Other evidence indicates that autophagy's survival effects may actually help breast cancer cells persist and contribute to chemotherapy resistance in the body.

https://www.novapublishers.com/catalog/product_inf...

It seems like nearly every time I find an article about some treatment that helps stop cancer cells, I find another article that states just the opposite or negates the findings of the first scientist. Like one scientist said fasting should absolutely help the body kill cancer cells, but another scientist said it does not help if you have hormone-dependent cancers, like some breast cancer and prostate cancer and is actually risky in hormone-dependent cancers. That doctor said chronic calorie restriction helps, but not fasting. I was all set to go on a fast.

Maybe the type of chloroquine these scientists use or the amount of it makes a difference? Or maybe there's more to it.

aliana0

Differing autophagy effects and survival mechanisms of ductal carcinoma in situ (DCIS) and microinvasive or invasive ductal carcinoma (IDC).

FROM THE FOLLOWING ARTICLE:

The two faces of autophagy and the pathological underestimation of DCIS

Ke-Da Yu & Zhi-Ming Shao

http://www.nature.com/nrc/journal/v11/n8/fig_tab/n...

According to this study, chloroquine and inhibiting autophagy could work in DCIS, but might actually potentially make things worse in invasive ductal carcinoma. I don't know if they are sure it might cause tumorigenesis in IDC or have good reason to suspect it could.

Reckless

I've been taking plaquenil (hydroxychloroquine) for the last 5 years, 200 mg/day. Still developed cancer. It's IDC, but likely was at DCIS, if not ADH stage 5 years ago. And I took D3 for much of that period too. Obviously, did not stop my cancer

aliana0

Reckless, so sorry that all that time on it didn't stop it.

Here's another article about autophagy, with some videos.

Disrupting autophagy, a cellular housekeeping process, limits cancer spread

"We began by asking, what would happen if we shut down autophagy in metastatic cancer cells," Macleod said. Two MD/PhD students working in MacLeod's laboratory, Marina Sharifi and Erin Mowers, noticed that when they placed metastatic breast cancer cells on a dish and monitored them with time-lapse microscopy, the control cells were "active, constantly moving around the dish," MacLeod said. But cancer cells that the team had altered, by knocking down autophagy-related genes Atg5 and Atg7, "didn't move at all. They appeared to be stuck."

"They literally just get stuck," MacLeod said. "Through the microscope, you can see the cell wobbling, trying to move, to put out new protrusions, to migrate. But it can't, because it is stuck, unable to dissolve the adhesions at the back end of the cell. Basically, autophagy-deficient tumor cells cannot migrate and as a result cannot travel to another location. This is why we think that inhibiting autophagy could block tumor metastasis."

http://medicalxpress.com/news/2016-05-disrupting-a...

Maybe these different groups of scientists are using different chemicals. Maybe some are using chloroquine, some are using chloroquine with something else or more than a couple of drugs, and some are using other drugs instead of chloroquine or enzymes or something else that block the cells. If these experiments turn out to work as they expect, then maybe blocking autophagy can work for DCIS or for any stage to stop the growth of the cells. Maybe there is a different form of chloroquine that is chemically different from Plaquenil that they are using?

Lisa123456

I just wanted to give an update on my research and address some points: it seems that the Chloroquine treatment for stage 0 cancers (DCIS and, I assume, LCIS) is dose-depended: 250 mg/week or 500 mg/week for 4 weeks. For invasive BC this treatment is not suitable; it could, actually, do harm because cell self-eating is beneficial for invasive BC and should be promoted (for example, by fasting) but detrimental to non-invasive cancers and should be inhibited (for example, by chloroquine).

It's interesting to hear that some of you already took chloroquine for different reasons and it didn't stop cancers from developing / spreading. It could be the dose or a fact that the cancer was already invasive when the medication was taken.

Regarding my DIY treatment: at this point, I'm not sure I can do it because I've just received my MRI results and there were some suspicious findings in my "good" breast. I'm scheduled for a followup mammogram + ultrasound + needle biopsy in 10 days. If they find invasive cancer, then I won't do the chloroquine, but will, probably, have BMX instead.

exbrnxgrl

I regularly took chloroquine more than 30 years before my dx and my bc is grade 1, quite indolent. Don't think the cancer even existed as invasive or otherwise, at that point

Lisa123456

That's good to know. I haven't come across any information on chloroquine preventing future cancers. If there are no malignant cells, then there's no cell self-eating to inhibit.

aliana0

Here is a Drug Bank paper on Chloroquine:

http://www.drugbank.ca/drugs/DB00608

If chloroquine can stop the cells from metastasis, as it did it that mini-video, then maybe it can help people with breast cancer at any stage by making it impossible for the cancer to continue to move toward and infect or invade other cells. If it can't keep moving, growing and spreading, and if it can't copy itself or reproduce as it normally does, then it would would sit "stuck" and couldn't infect other cells. Chloroquine makes the cells more sensitive to chemo and radiation. Maybe Plaquenil is not the same form of chloroquine that scientists are using or maybe they are combining chloroquine with other drugs or enzymes and it is the combination of drugs that is making cancer cells get "stuck"? Maybe it couldn't use self-cannibalism (autophagy) to keep the cancer organism thriving if it was sort of glued to one place and couldn't move around. Scientists are also working on ways to coax cancer cells out of the bone marrow so chemo and radiation can kill them. Apparently, they can hide out there and are somehow protected from chemo and radiation while hiding there.

Chloroquine: Mode of Action
http://science.sciencemag.org/content/151/3708/347...

Use of chloroquine to treat metabolic syndrome
https://www.google.com/patents/US8440695

If chloroquine is used to treat metabolic syndrome, then it must effect glucose and insulin levels in the blood. Doctor Otto Warburg said cancer uses glucose to thrive. (I was wrong when i wrote he knew much about cancer cells circa 1930/1931, he already knew in the early 1920's)

How cancer cells fuel their growth

https://www.sciencedaily.com/releases/2016/03/1603...

Malaria medicine chloroquine inhibits tumor growth, metastases, study shows
https://www.sciencedaily.com/releases/2014/08/1408...

Someone already wrote about this, but I am including it here. A Doctor Pedersen, who studied what Doctor Warburg found, and his colleagues, used 3-bromopyruvate to eliminate cancer cells.

3-Bromopyruvate (3BP) a fast acting, promising, powerful, specific, and effective "small molecule" anti-cancer agent taken from labside to bedside: introduction to a special issue."

Although the "Warburg effect", i.e., elevated glucose metabolism to lactic acid (glycolysis) even in the presence of oxygen, has been recognized as the most common biochemical phenotype of cancer for over 80 years, its biochemical and genetic basis remained unknown for over 50 years. Work focused on elucidating the underlying mechanism(s) of the "Warburg effect" commenced in the author's laboratory in 1969. By 1985 among the novel findings made two related most directly to the basis of the "Warburg effect", the first that the mitochondrial content of tumors exhibiting this phenotype is markedly decreased relative to the tissue of origin, and the second that such mitochondria have markedly elevated amounts of the enzyme hexokinase-2 (HK2) bound to their outer membrane. HK2 is the first of a number of enzymes in cancer cells involved in metabolizing the sugar glucose to lactic acid. At its mitochondrial location HK2 binds at/near the protein VDAC (voltage dependent anion channel), escapes inhibition by its product glucose-6-phosphate, and gains access to mitochondrial produced ATP. As shown by others, it also helps immortalize cancer cells, i.e., prevents cell death. Based on these studies, the author's laboratory commenced experiments to elucidate the gene basis for the overexpression of HK2 in cancer. These studies led to both the discovery of a unique HK2 promoter region markedly activated by both hypoxic conditions and moderately activated by several metabolites (e.g., glucose), Also discovered was the promoter's regulation by epigenetic events (i.e., methylation, demethylation). Finally, the author's laboratory turned to the most important objective. Could they selectively and completely destroy cancerous tumors in animals? This led to the discovery in an experiment conceived, designed, and conducted by Young Ko that the small molecule 3-bromopyruvate (3BP), the subject of this mini-review series, is an incredibly powerful and swift acting anticancer agent. Significantly, in subsequent experiments with rodents (19 animals with advanced cancer) Ko led a project in which 3BP was shown in a short treatment period to eradicate all (100%). Ko's and co-author's findings once published attracted global attention leading world-wide to many other studies and publications related to 3BP and its potent anti-cancer effect. This Issue of the Journal of Bioenergetics and Biomembranes (JOBB 44-1) captures only a sampling of research conducted to date on 3BP as an anticancer agent, and includes also a Case Report on the first human patient known to the author to be treated with specially formulated 3BP. Suffice it to say in this bottom line, "3BP, a small molecule, results in a remarkable therapeutic effect when it comes to treating cancers exhibiting a "Warburg effect". This includes most cancer types.

http://www.ncbi.nlm.nih.gov/pubmed/22382780

I think they had some trouble with 3-bromopyruvate being too toxic. Maybe they are working on ways around that.

Pyruvate is involved in that Warburg glucose to lactic acid fermentation.

http://www.icr.org/article/glycolysis-alcoholic-fe...

Lisa123456

Good research, aliana0. I've just found an article that says that some tumor's acidity prevent chloroquine from inhibiting autophagy (see Chloroquine: Acidic tumor pH inhibits drug effect ). However, the effect of disruption of the tumor's blood supply still seems valid.

aliana0

Thanks for the info! Doctor Warburg said: ""Cancerous tissues are acidic, whereas healthy tissues are alkaline. Water splits into H+ and OH- ions, if there is an excess of H+, it is acidic; if there is an excess of OH- ions, then it is alkaline." How to make the tumor and the area around it alkaline so chloroquine would work well?

I'd be willing to try this chloroquine treatment.

"The extracellular pH (pHe) of tumor tissues is often acidic [1], and acidic metabolites, e.g. lactic acid caused by anaerobic glycolysis in hypoxia, seem to be the main cause. Accumulating evidence shows that an acidic microenvironment is a regulator of cellular phenotype."

"The "Warburg effect" is a well-accepted theory that says that tumors tend to produce lactate by using the anaerobic glycolytic pathway, even in the presence of sufficient oxygen, rather than oxidative phosphorylation for energy production [1]. High lactate levels indicate metastases, tumor recurrence, and prognosis in some cancer patients [6-9]."

"Acidic pHe is toxic to many cells, including tumors [138]. However, if tumors have successfully adapted to their condition, and use it for their own cellular activation, this increases drug resistance and leads to more aggressive behavior. Therefore, management of tumor pHe and inhibition of blockade of proton-sensing system are important in not only raising drug efficacy, e.g. mitoxantrone, but in preventing metastasis."

from: Acidic extracellular microenvironment and cancer

Yasumasa Kato1*, Shigeyuki Ozawa2 , Chihiro Miyamoto3 , Yojiro Maehata3 , Atsuko Suzuki1 , Toyonobu Maeda1 and Yuh Baba

"Mitoxantrone is used to treat certain types of cancer, mostly metastatic breast cancer, acute myeloid leukemia, and non-Hodgkin's lymphoma. It improves the survival rate of children suffering from acute lymphoblastic leukemia relapse.^[1]

The combination of mitoxantrone and prednisone is approved as a second-line treatment for metastatic hormone-refractory prostate cancer. Until recently this combination was the first line of treatment; however, a combination of docetaxel and prednisone improves survival rates and lengthens the disease-free period.^[2]

Mitoxantrone is a type II topoisomerase inhibitor; it disrupts DNA synthesis and DNA repair in both healthy cells and cancer cells by intercalation^[6] between DNA bases."

https://en.wikipedia.org/wiki/Mitoxantrone

"Chloroquine intercalates into DNA and protects cells against topoisomerase II (topo II) poisons such as etoposide by hindering the DNA cleavage reaction of this target enzyme."

Inhibitors of topoisomerase II as pH-dependent modulators of etoposide-mediated cytotoxicity.

Langer SW1, Schmidt G, Sørensen M, Sehested M, Jensen PB.

http://www.ncbi.nlm.nih.gov/pubmed/10537359

Neutralizing tumor acidic environment improves immune-targeting therapies

Sodium bicarbonate combined with PD-1 or CTLA-4 Inhibitors or adoptive T-cell transfer reduces melanoma and pancreatic tumor growthH.

Lee Moffitt Cancer Center & Research Institute

https://www.sciencedaily.com/releases/2016/03/1603...
The acidity of the tumor microenvironment is a mechanism of immune escape that can be overcome by proton pump inhibitors (like Nexium?)

http://www.tandfonline.com/doi/full/10.4161/onci.2...

Michelle49

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Nasikg

Does anyone know the results of that study back in 2016?

LoriCA

Here you go Nasikg - http://cancerres.aacrjournals.org/content/77/13_Supplement/CT140

It was a small study of only 12 patients. 7/12 patients exhibited a reduction in lesion diameter by MRI, 3/12 patients exhibited no measurable change, and 2/12 had a slight increase.

blah333

I tried this, there is a malaria drug/supplement you can get called

Artemisinin

it did not make my DCIS shrink or disappear in the month+ I took between diagnosis and my MRI. That's all the time I had. Waste of money. Pharmaceutical companies can probably make a more potent version at some point but DCIS cells can always reappear. I can't imagine trying to take this the rest of your life or having a lapse due to insurance or stop taking vitamins and then have a more invasive cancer. I don't know. But something better needs to be done than mastectomies and lumpectomies/messing up our bodies

Nasikg

Thank you LoriCa! This is very helpful