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Metformin as anti-cancer agent

carolenk's picture
carolenk
Posts: 909
Joined: Feb 2011

Metformin is used for polycystic ovarian syndrome & for type 2 diabetics. Here's more interesting information on metformin.

Just curious if any of the survivors were taking Metformin before they were diagnosed with OVCA? Or does Metformin (Glucophage) protect women from OVCA?

I know the info is REALLY technical, but the last paragraph is enough to understand.

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Metformin as Anticancer Drug
The discovery of LKB1 as the tumor suppressor gene responsible for Peutz-Jegher syndrome, an autosomal-dominant disorder characterized by melanocytic macules of the lips, multiple gastrointestinal hamartomatous polyps, and an increased risk for various neoplasms including gastrointestinal cancer led to the suspicion that metformin may exhibit antitumor properties, because LKB1 is an upstream AMPK regulator [264]. These observations were supported by two reports linking treatment with metformin in patients with diabetes with a lower risk of cancer [265,266].

A number of experimental data indicate that metformin AMPK exerts its antitumor actions by activating AMPK. This serine/threonine kinase consists of a heterotrimeric complex comprising a catalytic α subunit and regulatory β and γ subunits [267]. AMPK is activated under conditions that deplete cellular ATP and elevate AMP levels such as glucose deprivation, hypoxia, ischemia, and heat shock, which are associated with an increased AMP/ATP ratio [268]. AMPK actions appear to be mediated by means of multiple mechanisms. AMPK activation leads to cell cycle arrest via p53-p21 axis up-regulation, although Cyclin D1 down-regulation may also occur independently of AMPK activation [269] and protein synthesis-regulation inhibition of the TSC2-mTOR (mammalian target of rapamycin) pathway. In addition, AMPK activation impedes de novo fatty acid synthesis, specifically the generation of mevalonate, as well as other products downstream of mevalonate in the cholesterol synthesis pathway. Thus, the AMPK signalling network contains a number of tumor suppressor genes including LKB1, p53, TSC,1 and -2, and overcomes growth factor signalling from a variety of stimuli (via growth factors and by abnormal regulation of cellular proto-oncogenes including PI3K, Akt, and ERK [270].

Recent studies have reported that extracellular hormonal stimulation by adiponectin and leptin, both of which are adipose tissue-secreted peptide hormones, also could activate AMPK [271]. Adiponectin has been reported to inhibit vascular SMC proliferation [272]. Plasma adiponectin has been shown as decreased in patients with carcinomas from breast, endometrium, and stomach [273-275]. Interestingly, potential anticancer effects of adiponectin have been demonstrated in breast and endometrial cancer cells [276,277].

Thus, metformin exhibits pleiotropic effects on cancer cells as reflected by its antitumor effects in a wide variety of cancer cell lines in vitro and in vivo including breast, glioma colon, ovarian, and prostate [278-281]. Whether their antitumor actions depend on AMPK activation or whether these are independent of this pathway requires further study. What is clear, however, is that metformin possesses full potential as a cancer drug that should be fully evaluated in pre-clinical and clinical studies.

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If you read the glucosamine thread that I posted, you will find the AMPK pathway mentioned in that article, too.

Here the link to the web site for more info where there is a lot of info on commonly used drugs that may have an "off-label use" as anti-cancer agents.

http://www.molecular-cancer.com/content/7/1/82

Carolen

Tethys41's picture
Tethys41
Posts: 1057
Joined: Sep 2010

interested in hearing whether anyone was using this drug prior to diagnosis, as I am plannig to start taking it to control my insulin resistance.

carolenk's picture
carolenk
Posts: 909
Joined: Feb 2011

I was thinking starting on Metformin, too, as I also have a mild problem with insulin resistance...it is supposed to help weight loss, too.

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001

Dr. Herman Kattlove, former medical editor for the American Cancer Socity, wrote in his private blog that he read an recent article touting the benefits of metformin (glucophage) in preventing cancer.

From what he gleamed in the article, almost all the evidence for cancer prevention by metformin comes from studies of people with diabetes. Diabetics are known to have higher rates of certain cancers - liver, pancreas, endometrium, colon/rectum, breast and bladder.

The issues for the speculation why this happens is the higher blood sugar in diabetics - sugar feeds cancer. The other issue is the higher amounts of insulin in their blood. People with type 2 diabetes have higher than normal amounts of insulin in their blood and the problem is they can't use it properly - they are relatively insensitive to insulin.

A large study of metformin and cancer was published in the November 2010 issue of the journal, Cancer Prevention Reserach. It was a meta-analysis which the authors reviewed and reported on all the well-documented studies of metformin and cancer in diabetics. They found that diabetic patients treated with metformin were about 25% less likely to develop or die from the typical cancers found in diabetics.

The reason metformin reduces the cancer rate isn't known, however, scientists think it may be related to lower blood insulin levels or some interference with the cancer cells ability to use glucose. It is also known that metformin will slow cancer cell growth in test tubes and in mice.

The bigger issue Kattlove suggests is whether it will block cancer growth in non-diabetic people. Metformin is not an innocuous drug. It does interfere with metabolism - good for diabetics but who knows for non-diabetics?

NCI is sponsoring a study where metformin is being added to the usual drugs in patients with early stage breast cancer to prevent the cancer from coming back. Half the patients will get metformin and the rest will receive a placebo. It may take 5-10 years. In the meantime, he suggested forgetting about the drug. We just don't know if it will work and it may be harmful, unless you have adult-onset diabetes.

Tethys41's picture
Tethys41
Posts: 1057
Joined: Sep 2010

Oops, double post.

Tethys41's picture
Tethys41
Posts: 1057
Joined: Sep 2010

Thanks so much for the information. Do you have any knowledge as to whether it is beneficial to those patients with insulin resistance vs. diabetes?

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001

Diabetic patients with breast cancer had significantly higher rates of response to neoadjuvant chemotherapy if they taking metformin, data from a small retrospective analysis suggest.

Patients on the antidiabetic agent had a three-fold increased rate of pathologic complete response compared with diabetic patients not treated with metformin, and a 50% higher response rate compared with nondiabetic patients, Sao Jiralerspong, M.D., of the University of Texas M.D. Anderson Cancer Center in Houston, reported at a 2008 American Society of Clinical Oncology meeting.

The findings add to epidemiologic evidence that diabetic patients treated with metformin have a reduced risk of cancer and cancer-related mortality.

"This was a retrospective, hypothesis-generating study," said Dr. Jiralerspong. "Nonetheless, the results warrant further studies to evaluate the potential of metformin as an antitumor agent."

Laboratory studies have shown metformin inhibits the growth of breast cancer cells by activating AMP kinase and inhibiting the mTOR pathway and associated protein translation, said Dr. Jiralerspong.

The evidence provided a basis for the hypothesis that metformin's antiproliferative effect might enhance the efficacy of systemic neoadjuvant therapy in diabetic patients with breast cancer.

To examine the hypothesis in the clinical setting, Dr. Jiralerspong and colleagues retrospectively reviewed records on more than 2,500 breast cancer patients treated with neoadjuvant systemic therapy. The study population included 155 diabetic patients, 68 treated with metformin.

The primary outcome was pathologic complete response, defined as no residual disease in the breast or lymph nodes.

Among nondiabetic patients, 16% had a pathologic complete response, and diabetic patients not treated with metformin had a pathologic complete response rate of 8%.

In contrast, 24% of diabetic patients who were also taking metformin had pathologic complete responses (P=0.02 overall, P=0.007 versus diabetic patients without metformin, P=0.099 versus nondiabetic patients).

In a multivariate analysis adjusted for diabetes, treatment with metformin independently predicted an increased likelihood of pathologic complete response (OR 3.2, P=0.023).

At a median follow-up of 37 months, recurrence-free survival did not differ among the three groups.

However, nondiabetic patients had a significantly better (P=0.020) overall survival (85.9%) compared with diabetic patients treated with metformin (80.9%) or without metformin (77.6%).

American Society of Clinical Oncology 2008 Annual Meeting; Abstract 528

carolenk's picture
carolenk
Posts: 909
Joined: Feb 2011

This is very interesting information. What's missing in the research is the degree of glucose control in the diabetic patients.

If any of the ovarian cancer survivors (diabetic or non-diabetic) are STILL eating sugar, perhaps this information will convince them that sugar is the enemy. Perhaps one of the reasons why daily exercise has been shown to help reduce cancer risk/recurrence is because exercise lowers blood sugar.

The overall survival for the breast cancer patients compares favorably to the overall survival for ovarian cancer patients.

Carolen

gdpawel's picture
gdpawel
Posts: 549
Joined: May 2001

Carolen

"The ovarall survival for breast cancer patients compares favorably to the overall survival for ovarian cancer patients."

You can cut your chance of having breast cancer come back by 60% if you cut the fat in your diet by 30%. One of the hardest of all diet intervention studies has to be dietary intervention studies to reduce cancer.

A watershed study in the Journal of the National Cancer Institute suggested that women with estrogen receptor negative breast cancer can cut their recurrence rate by 60% if they stayed with a diet in which fewer than 20% of calories were from fat.

You can either wait for proof beyond reasonable doubt or you can go with the preponderance of evidence, which is that you can cut your chance of having cancer come back 60% if you cut the fat in your diet by 30%.

Source: Chlebowski, R. et al. Dietary Fat Reduction and Breast Cancer Outcome: Interim Efficacy Results From the Women's Intervention Nutrition Study J Natl Cancer Inst, Dec 2006; 98: 1767 - 1776

Greg

carolenk's picture
carolenk
Posts: 909
Joined: Feb 2011

Commercial animal fat is loaded with hormones and pesticides...I have to agree that eliminating commercial animal fat is a good idea for anyone dealing with cancer. I think there has to be distinction between made between good fat and bad fat.

There is also some research that shows cutting fat in the diet improves blood sugar control in type 2 diabetics.

Carolen

Radioactive34's picture
Radioactive34
Posts: 387
Joined: May 2011

I had PCOS prior to the hysterectomy. I was on metformin for years...10 plus prior to the diagnosis. I am not diabetic but was on it for the PCOS...somehow the way the body processes insulin plays into PCOS. I am still on metformin since PCOS is considered an endocrinological disorder versus a reproductive disorder. The PCOS is just a symptom.

There seems to be no more to remove me from metformin. I guess the reasoning is that even though the PCOS is gone, I still have the endocrine disorder...

Hissy_Fitz's picture
Hissy_Fitz
Posts: 1869
Joined: Sep 2009

Someone on the board (Clamryn?) is taking Metformin with the idea of preventing a recurrence. Whoever it is, they aren't diabetic.

I asked my doctor about it and he compared it to the idea a few years back of giving everyone Celebrex. He wouldn't prescribe it, as I don't have insulin resistance or diabetes. I did have PCOS when I was younger. I can't remember if I took Metformin for it or not.

Metformin is cheap and has almost zero side effects, making it truly a dream drug, if it works in helping prevent recurrence.

Carlene

carolenk's picture
carolenk
Posts: 909
Joined: Feb 2011

The problem with Celebrex was that it gave some people heart attacks. Otherwise, it was a pretty good anti-inflammatory drug.

poopergirl14052's picture
poopergirl14052
Posts: 1179
Joined: Nov 2010

and I am still taking it as I am diabetic. I have3 had one reocurrance . so it didn't work for me but it did kep my glucose stable even with steroids which tend to raise glucose . ait would be great if this drug worked for some people..val

carolenk's picture
carolenk
Posts: 909
Joined: Feb 2011

Just wondering if your HgbA1c was below 7% prior to your diagnosis of ovarian cancer and during your first remission. I found some research that showed Metformin worked better for suppressing cancer in combination with something called 2-deoxy D-glucose (something that blocked glycolysis)...but I think that drug is still experimental.

I like the idea of Metformin keeping glucose levels down despite steroid use.

Carolen

poopergirl14052's picture
poopergirl14052
Posts: 1179
Joined: Nov 2010

was 6.2 at the time..but now 7. My MD took me Actos as it may cause bladder cancer..val

EnglishGal's picture
EnglishGal
Posts: 101
Joined: Jul 2011

I was diagnosed as a type 2 diabetic in May of 2008 - May is a bad month for me (LOL as my surgery for ovarian cancer was performed in May of 2010! Beware the month of May!

I take Metformin and my A1C values run between 6 and 6.5.

Ann

carolenk's picture
carolenk
Posts: 909
Joined: Feb 2011

Dear EnglishGal

As I recall, you are in remission, right? Just wondering if you are able to exercise 5 days/week for at least 30 minutes at a time.

Carolen

EnglishGal's picture
EnglishGal
Posts: 101
Joined: Jul 2011

Yes, I am in remission, Carolenk, and I do exercise as much as I can.

carolenk's picture
carolenk
Posts: 909
Joined: Feb 2011

OK, Val, you gotta work on getting back to a HgbA1c of less than 6.5 again. I can imagine the neuropathy makes it hard to exercise and exercise is so good for keeping your blood glucose down. I wanna see you back in remission again, Sister!

Carolen

AussieMaddie's picture
AussieMaddie
Posts: 345
Joined: May 2011

Hi all :)

thouht I'd add my experience to the mix. Don't know that it will enlighten at all though. I was started on Metformin years ago not because I was diabetic but because I was considered to be pre-diabetic (glucose impaired?) because I was so big. My BMI was probably about 50. Since then, I lost 42kg on the weight loss drug Reductil (*everything* went down, including my blood sugar - no longer pre-diabetic, but not taken off the Metformin). Reductil blamed by one doctor for my needing a pacemaker a few months after it stopped working. In that time, I started putting back on all the weight. Up 32kg when I thought my distended stomach felt different, not going down in between food binges. So did my doctor. The next week, thinking "Nope, something *is* different" I saw a different doctor, who sent me for an ultrasound. "10kg fluid in abdomen". *That's* why it wasn't going down. Into hospital. Ascites. Cancer of the peritoneaum, but primary considered to be elsewhere, just "unknown". Drained of fluid, lost more weight in hospital (couldn't binge) and down to my lowest of 85kg. Started on chemo, not sick from that so bingeing started up again in earnest - high in sugar and particularly fats, the whole time still on Metformin. Still am. And now I'm getting closer to the weight I had before the Reductil. CT scans at start of chemo showed no sign at all of any kind of tumour. Only the fluid (ascites) was seen to carry the cancer. A PET scan taken a couple of months ago approx. surprisingly also showed abosolutely nothing.

Might the Metformin have anything to do with my complete lack of the evidence of tumours?

The CA125 has been slowly climbing since before I finished the chemo about two months ago. Onc. says it because it has stopped being effective. Wating to see how it goes at present. Still no symptoms yet (except possibly for a twinge one or twice in the left pelvic area over the past month)

Am kept on Metformin only because of my size and my bingeing, but more often than not I forget to take the 2nd one.

Don't know that it has helped cause a lack of symptoms from the cancer or not. But if diet is a cause, then I should be long gone!

AussieMaddie

poopergirl14052's picture
poopergirl14052
Posts: 1179
Joined: Nov 2010

I may be finally able to go back to the YMCA and resumes my water aroebics class and maybe zumba. My Dr gave me some lidocaine cream to rub on my feet. I tried some at work the other night and It helped me make it through the rest of my shift. I am hoping to get my A1C back down to 6,,,,,,wish me luck...val

EnglishGal's picture
EnglishGal
Posts: 101
Joined: Jul 2011

Hi Val, I am taking zumba and really love it. It is a really great workout and gets you sweating and your heart pounding. Good luck on getting your A1C down to 6. I know you will do it!

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