The Leukemia & Lymphoma Society - Fighting Blood Cancers
13 Replies Latest reply: Apr 8, 2012 7:54 PM by GerryL RSS

Interesting press on B-catenin inhibitors

CallMeLucky Registered Users
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Researchers reporting in the April Cell Stem Cell, a Cell Press publication, have found a way to stop leukemia stem cells in their tracks. The advance in mice suggests that a combination approach to therapy might stamp out chronic myeloid leukemia (CML) for good.

That's in contrast to the vast majority of CML patients taking drugs like imatinib (aka Gleevec) today, who often go into remission only to see their cancer return again. It is those lingering leukemia stem cells, which stubbornly resist existing therapies, that fuel the cancer's comeback.

 

"Imatinib inhibits the oncoprotein [that drives CML] and it is incredibly effective at putting patients into remission," said Scott Armstrong of Harvard Medical School. "But there is growing evidence that this doesn't rid the body of the most immature cancer cells. The question is: How can we eradicate those cells?"

 

The Cell Stem Cell study focused on a pathway known to be important in blood stem cells during development but not in adulthood. The new findings in mice suggest that leukemia stem cells revert back to their dependence on that early developmental pathway.

 

That leaves leukemia stem cells vulnerable to treatments aimed at the so-called β-catenin pathway in a way that normal blood stem cells aren't. The evidence shows that imatinib plus the loss of β-catenin can help to prevent recurrence of the disease. β-catenin inhibitors given to mice also helped to eliminate leukemia stem cells, as did a pain-relieving drug already in use that lowers β-catenin levels, if indirectly.

 

Armstrong says there is more work to do to ensure that β-catenin blockers would work in the same way in humans that they do in the mice. If so, it's likely CML patients won't be the only or even the first to gain from the new treatment strategy.

 

"It will take time because people with CML already do pretty well," he says. But β-catenin inhibitors might be just what the doctor ordered in the case of some other, harder-to-treat forms of leukemia, in colon cancer, or perhaps in patients who have entered an acute stage of CML.

 

"The appeal is that this pathway is important for the leukemia, but not for normal cells," Armstrong says. "It gives us an angle for therapy." A drug targeted at β-catenin might just get rid of leukemia and its stem cells once and for all, while leaving healthy blood stem cells unscathed.

More information: Heidel et al.: "Genetic and Pharmacologic Inhibition of β-Catenin Targets Imatinib-Resistant Leukemia Stem Cells in CML." Cell Stem Cell - April 6, 2012 print issue. DOI:10.1016/j.stem.2012.02.017

Provided by Cell Press

  • Re: Interesting press on B-catenin inhibitors
    scuba Registered Users
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    This has been known for some time now: http://www.sciencedaily.com/releases/2010/12/101213121704.htm

    and is also a major reason why I take Curcumin in high doses (see link below).

     

    I am encouraged that β-catenin inhibitors as cited in the article you posted, along with what we have learned about Omega-3 EPA derivatives earlier may help augment TKI action so that CML can be arrested at the stem cell level.

     

    On a personal note, I will have a PCR test done next month. I am very eager to learn if my 20mg. Sprycel dose is able to add zero's to my last PCR reading if not outright PCRu (CMR). I don't believe Dr. Cortes has any patients that are PCRu on 20mg. Sprycel. He wrote me that he has many patients who are "responding" and "doing very well", but none that are PCRu at that dose. My rate of decline leading to MMR was noteworthy to him.

     

    I believe that Curcumin's known inhibition of β-catenin may be a contributing factor:

    http://www.ncbi.nlm.nih.gov/pubmed/15893313

     

    And when I go off Sprycel ( and I WILL), perhaps the Curcumin can keep me in remission on its own - even if I don't get to CMR. If my PCR gets to a stable very low level, I will try TKI interruption and test whether PCR goes up or not while staying on Curcumin.

     

    (p.s. Don't get Curcumin on your clothes....very bad)

    • Re: Interesting press on B-catenin inhibitors
      CallMeLucky Registered Users
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      Michael,

       

      What is the link to the Curcumin you purchase? You posted it once before but I couldn't find it.

    • Re: Interesting press on B-catenin inhibitors
      Dina36 Registered Users
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      Michael,

      Can you please tell me what's Curcumin and why do you take it?

      Thanks!

    • Re: Interesting press on B-catenin inhibitors
      pamsouth Registered Users
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      scuba wrote:

       

      This has been known for some time now: http://www.sciencedaily.com/releases/2010/12/101213121704.htm

      and is also a major reason why I take Curcumin in high doses (see link below).

       

      I am encouraged that β-catenin inhibitors as cited in the article you posted, along with what we have learned about Omega-3 EPA derivatives earlier may help augment TKI action so that CML can be arrested at the stem cell level.

       

      On a personal note, I will have a PCR test done next month. I am very eager to learn if my 20mg. Sprycel dose is able to add zero's to my last PCR reading if not outright PCRu (CMR). I don't believe Dr. Cortes has any patients that are PCRu on 20mg. Sprycel. He wrote me that he has many patients who are "responding" and "doing very well", but none that are PCRu at that dose. My rate of decline leading to MMR was noteworthy to him.

       

      I believe that Curcumin's known inhibition of β-catenin may be a contributing factor:

      http://www.ncbi.nlm.nih.gov/pubmed/15893313

       

      And when I go off Sprycel ( and I WILL), perhaps the Curcumin can keep me in remission on its own - even if I don't get to CMR. If my PCR gets to a stable very low level, I will try TKI interruption and test whether PCR goes up or not while staying on Curcumin.

       

      (p.s. Don't get Curcumin on your clothes....very bad)

      Scuba where do you get the Curcumin, does it work with Gleevec or Tasigna?

       

      PamSouth

      • Re: Interesting press on B-catenin inhibitors
        scuba Registered Users
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        To: Dina, Pat and Pam,

         

        Curcumin is from the Tumeric root. It is what gives Curry its yellow color and taste. Essentially, Curcumin is a plant. I learned about Curcumin from reading about CML and in discussions with a few medical friends of mine as well as the blog, "Margaret's Corner", you cited Pat.

         

        I added Curcumin to my diet slowly - about 2 grams per week until I was up to the 8 gram mark of 95% Curcumin extract. Since then I have dialed back my dose to 4 grams per day by substituting a more bio-available Curcumin called Curcumin C3 complex with Piperine. The Piperine is a pepper extract (another plant ... see a trend here) which increases the absorption of Curcumin into the blood. I am also experimenting with an enteric coated Curcumin which causes the Curcumin to bypass the stomach and dissolve in the small intestine - further increasing bio-availability.

         

        There is no doubt about Curcumin's medicinal benefits in the petri dish. The problem is it is not bio-available (cross the stomach blood boundary) easily. This is why 8 grams of the stuff is needed for cancer benefits to be observed.

         

        As I am not a doctor, you should consult with your own doctor about Curcumin. I am my own guinnea pig with no governing law controlling me (yet) - so I get to try things without getting approval (*except from my wife - without her approval life gets unpleasant). When I learned that Sprycel + Curcumin improved response in Colon cancer than Sprycel did alone (http://www.ncbi.nlm.nih.gov/pubmed/20473900), I decided to combine the two and see if I get benefit for CML. I figured it can't harm me since the Colon people had no trouble taking both.

         

        I have been on Curcumin + 20mg. Sprycel for almost a year now - but I started Curcumin before I started my current Sprycel regimen. Dr. Cortes is my CML doctor and I let him know everything I do. He does not tell me not to...and he does not encourage me regarding Curcumin.

         

        It is my belief that Curcumin is indeed augmenting the Sprycel's effectiveness. If nothing else - I get to take much less drug (i.e. no side affects) and still get a great CML response that would normally require a much higher dose.

         

        There is no science here to what I am doing. I am my own trial. There is enough evidence to my satisfaction that Curcumin messes with B-catenin,

        NF-kappa B and other proteins that CML cells need to survive that I believe it helps.

         

        My goal is to get to PCRu and then go off Sprycel to see if I can stay PCRu. I want to be clear. I am not going to wait two years after achieving PCRu. If next month I am PCRu - I am done with Sprycel. I will just keep taking my Curcumin. I am concerned about long term Sprycel's affect on the body. And then I test 3 months later and see if I remain PCRu. If I don't - then back on my 20mg. Sprycel.

         

        That's my plan.

         

        p.s. Curcumin is great for arthritis. I had the beginnings of it in my hand for several years (family heredity) and then after I started Curcumin - in about 3 months - gone. No arthritis at all. So - it seems CML did have a silver lining for me....it led me to Curcumin.

      • Re: Interesting press on B-catenin inhibitors
        GerryL Registered Users
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        Just a couple of things with Curcumin -

        A lot of the web sites don't recommend you take it if you are on a blood thinner or suffer from gall bladder.

        I did start taking Curcumin (at the lowest dose) to see if it helped with my joint/muscle pain, no luck obviously not arthritis but Gleevec related. The other thing I noticed I've had a few bruises appear lately, hadn't put it down to anything until I looked at Wikipedia - "More recently, curcumin was found to alter iron metabolism by chelating iron and suppressing the protein hepcidin, potentially causing iron deficiency in susceptible patients."

        I've stopped taking the Curcumin.

        I wish Michael all the luck if he can get to PCRU and maintain it with the Curcumin.

        • Re: Interesting press on B-catenin inhibitors
          scuba Registered Users
          Currently Being Moderated

          Hi Gerry,

           

          In response to your concerns about iron depletion and Curcumin. Below is a link to "Margaret's Blog". She has Multiple Myeloma (MM) and uses Curcumin alone to treat it. She is not a scientist, but reports on studies she comes across such as the one on Iron depletion and Curcumin. It is worth reading. I contacted her early in my Curcumin taking days regarding the issue cite above.

           

          http://margaret.healthblogs.org/life-with-myeloma/discovery-of-curcumin/curcumin-and-iron/

           

          What is important is that Curcumin has strong anti-cancer properties (blood especially), and that the iron deficiency you note is only a problem for people who already have an iron problem before taking Curcumin. I have been taking Curcumin for more than a year. My red blood and related markers for anemia are on the low side of normal and have been that way since diagnosis and before Curcumin. I have increased my meat intake (I was largely a veggie person before) to make sure I have plenty of dietary iron. Other than that - I am concerned much more about deadly leukemia than Curcumin.

           

          Curcumin's benefits are well documented. I will continue to take Curcumin with my Sprycel until I am PCRu (hopefully). And then I will take Curcumin alone.

           

          Your joint/muscle pain due to Gleevec may possibly be managed with increasing your Magnesium levels (400-800mg per day). When I was on Gleevec and developed the muscle cramps/pain, I took extra Magnesium and that helped tremendously. I continue to take Magnesium regularly as I switched from Gleevec to Sprycel.

           

          And I continue to take Curcumin.

          • Re: Interesting press on B-catenin inhibitors
            GerryL Registered Users
            Currently Being Moderated

            Hi Michael,

            When my first BMB was done my doc commented to me that I had no iron stored in my bone marrow - due more I think to my heavy menstrual cycle then CML. As I haven't gone through menopause yet and though I am on an iron tablet, I don't think the issue has resolved itself. In a couple of years, if they haven't come up with a cure and my iron levels are normal I will probably give Curcumin another go. By then I will have reduced my Gleevec dosage and be looking to have a go at coming off it. I achieved PCRU at my last blood test and hopefully will back that up with my next test in May. If I can do that I will talk to my doctor about a dosage reduction at 1 year. I know two years is the magic number but I'm going to try for 300mg and see how that goes. Mind you I have yet to discuss this with my doc.

            I was taking a magnesium supplement prior to diagnosis, but have noticed that the joint/muscle issues have gotten worse in the last six months. Perhaps since I have a low level of leukemia cells floating around in my body, the Gleevec is off creating havoc elsewhere. I think a dosage reduction will be the thing that helps.

             

            I have been following your journey with interest and keep my fingers crossed that you achieve you goal.

  • Re: Interesting press on B-catenin inhibitors
    ChrisC Registered Users
    Currently Being Moderated

    So glad that this appears promising! I wouldn't mind a nice "enforcer" follow up to run through the system to ensure that any lingering baddies have been snuffed out.

     

    Re curcumin / turmeric on the clothes, do put the stained part out in the sun or inside in a sunbeam: the sun fades the stain in a few hours.

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