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Posted by: thepinetree on 10/15/2017 10:05 AM Updated by: thepinetree on 10/15/2017 10:08 AM
Expires: 01/01/2022 12:00 AM
:

Novel Treatment Causes Cancer to Self-Destruct Without Affecting Healthy Cells

Bronx, NY...Scientists at Albert Einstein College of Medicine have discovered the first compound that directly makes cancer cells commit suicide while sparing healthy cells. The new treatment approach, described in today’s issue of Cancer Cell, was directed against acute myeloid leukemia (AML) cells but may also have potential for attacking other types of cancers.




Researchers, led by Evripidis Gavathiotis, Ph.D., at Albert Einstein College of Medicine have discovered the first compound that directly makes cancer cells commit suicide while sparing healthy cells. Evripidis Gavathiotis, Ph.D.“We’re hopeful that the targeted compounds we’re developing will prove more effective than current anti-cancer therapies by directly causing cancer cells to self-destruct,” says Evripidis Gavathiotis, Ph.D., associate professor of biochemistry and of medicine and senior author of the study. “Ideally, our compounds would be combined with other treatments to kill cancer cells faster and more efficiently—and with fewer adverse effects, which are an all-too-common problem with standard chemotherapies.”

AML accounts for nearly one-third of all new leukemia cases and kills more than 10,000 Americans each year. The survival rate for patients has remained at about 30 percent for several decades, so better treatments are urgently needed.

The newly discovered compound combats cancer by triggering apoptosis—an important process that rids the body of unwanted or malfunctioning cells. Apoptosis trims excess tissue during embryonic development, for example, and some chemotherapy drugs indirectly induce apoptosis by damaging DNA in cancer cells.

Apoptosis occurs when BAX—the “executioner protein” in cells—is activated by “pro-apoptotic” proteins in the cell. Once activated, BAX molecules home in on and punch lethal holes in mitochondria, the parts of cells that produce energy. But all too often, cancer cells manage to prevent BAX from killing them. They ensure their survival by producing copious amounts of “anti-apoptotic” proteins that suppress BAX and the proteins that activate it.


This image depicts the structure of the BAX protein (purple). The activator compound BTSA1 (orange) has bound to the active site of BAX (green), changing the shape of the BAX molecule at several points (shown in yellow, magenta and cyan). BAX, once in its final activated form, can home in on mitochondria and puncture their outer membranes, triggering apoptosis (cell death).


“Our novel compound revives suppressed BAX molecules in cancer cells by binding with high affinity to BAX’s activation site,” says Dr. Gavathiotis. “BAX can then swing into action, killing cancer cells while leaving healthy cells unscathed.”

Dr. Gavathiotis was the lead author of a 2008 paper in Nature that first described the structure and shape of BAX’s activation site. He has since looked for small molecules that can activate BAX strongly enough to overcome cancer cells’ resistance to apoptosis. His team initially used computers to screen more than one million compounds to reveal those with BAX-binding potential. The most promising 500 compounds—many of them newly synthesized by Dr. Gavathiotis’ team—were then evaluated in the laboratory.

“A compound dubbed BTSA1 (short for BAX Trigger Site Activator 1) proved to be the most potent BAX activator, causing rapid and extensive apoptosis when added to several different human AML cell lines,” says lead author Denis Reyna, M.S., a doctoral student in Dr. Gavathiotis’ lab. The researchers next tested BTSA1 in blood samples from patients with high-risk AML. Strikingly, BTSA1 induced apoptosis in the patients’ AML cells but did not affect patients’ healthy blood-forming stem cells.
“We’re hopeful that the targeted compounds we’re developing will prove more effective than current anti-cancer therapies by directly causing cancer cells to self-destruct.”

– Evripidis Gavathiotis, Ph.D.

Finally, the researchers generated animal models of AML by grafting human AML cells into mice. BTSA1 was given to half the AML mice while the other half served as controls. On average, the BTSA1-treated mice survived significantly longer (55 days) than the control mice (40 days), with 43 percent of BTSA1-treated AML mice alive after 60 days and showing no signs of AML.

Importantly, the mice treated with BTSA1 showed no evidence of toxicity. “BTSA1 activates BAX and causes apoptosis in AML cells while sparing healthy cells and tissues—probably because the cancer cells are primed for apoptosis,” says Dr. Gavathiotis. He notes that his study found that AML cells from patients contained significantly higher BAX levels compared with normal blood cells from healthy people. “With more BAX available in AML cells,” he explained, “even low BTSA1 doses will trigger enough BAX activation to cause apoptotic death, while sparing healthy cells that contain low levels of BAX or none at all.”

Plans call for Dr. Gavathiotis and his team to see whether BTSA1 will show similar effectiveness when tested on animal models of other types of cancer.

The paper, “Direct activation of BAX by BTSA1 overcomes apoptosis resistance in acute myeloid leukemia,” was published October 9 in Cancer Cell. In addition to Dr. Gavathiotis and Mr. Reyna, other Einstein researchers involved in the study were Thomas P. Garner, Ph.D., Andrea Lopez, M.S., Felix Kopp, Ph.D., Gaurav S. Choudhary, Ph.D., Ashwin Sridharan, M.D., Swathi-Rao Narayanagari, M.S., Kelly Mitchell, M.S., Baoxia Dong, Ph.D., Boris A. Bartholdy, Ph.D., Amit Verma, MB.B.S., and Ulrich Steidl, M.D., Ph.D.

Funding for this research was provided by the National Cancer Institute (NCI), part of the National Institutes of Health (R01CA178394), and awards from the Sidney Kimmel Foundation for Cancer Research, the Gabrielle’s Angels Foundation for Cancer Research, and the Pershing Square Sohn Cancer Research Alliance. Partial support was also provided by the Albert Einstein Cancer Center, which is funded by the NCI (P30CA013330).


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No Subject
Posted on: 2017-10-15 10:17:06   By: Anonymous
 
Gee, guess all those hippies won't need their dope "medicine" anymore 😆

[Reply ]

    Re: What a halarious person you think you are
    Posted on: 2017-10-15 11:00:43   By: Anonymous
     
    Gee, I guess you're an idiot and never lost a love one to cancer or worse yet, watch a loved one slowly waste and suffer until their last dying days. To see kids wondering why their Mother can't get better, take them to school, or even get up in the morning happy and full of life as she once was.
    Yet here you are, thinking you're being funny.
    If ignorance is bliss you must be the dumbest, happiest fool God has ever put on the planet. I hope you never have the misfortune to have someone you care about die from cancer.


    [Reply ]

      Re: What a halarious person you think you are
      Posted on: 2017-10-15 12:23:20   By: Anonymous
       
      Hey, waste case, everybody have family members who struggle, and all to often, die. Been happening ever since the bitch got bored and danced with the serpent.

      Dope is just more poison from the devil. Provided to derail the weak and the deliberately ignorant.

      Free your mind. Try being sober for just one week. You would be amazed at just what a beautiful and abundant world we have been blessed with.

      And, yes, real doctors will apply the results of real scientists, who will unlock the secrets of the bodies we have been loaned, and thereby lessen the wrath and indignities of age and disease. Your bug poison will play no roll in it whatsoever.

      Wake up and get a life.

      [Reply ]

        Re: What a halarious person you think you are
        Posted on: 2017-10-15 17:22:50   By: Anonymous
         
        Except that under Trump, science grants are being cut. Politics aside, this is a remarkable breakthrough and gives hope to many who know just how horrific a disease cancer is.

        [Reply ]

        Re: What a halarious person you think you are
        Posted on: 2017-10-16 06:15:57   By: Anonymous
         
        gee, really? Hey everybody, please meet the next Einstein
        He has found the secret all mankind has never known, he, himself, has found out.....get ready, drum roll please.....people die.
        wow thanks Mr Scientist!!!!!

        [Reply ]

        Re: What a halarious person you think you are
        Posted on: 2017-10-16 06:55:58   By: Anonymous
         
        Take another toke dude, I don't drink or smoke.
        Find the Lord or something that might humble you, sounds like you like gloating and assuming things of people you know nothing about, their walk in this life.
        ASS u me....and I'm sure a small mind can put together that, if not bummer for everyone ASSociated with you.
        Have a beautiful day everyone

        [Reply ]

FABULOUS!
Posted on: 2017-10-15 15:07:15   By: Anonymous
 
This is fabulous news - let's hope it gets in use quickly!

[Reply ]

Thanks to science!
Posted on: 2017-10-15 16:43:40   By: Anonymous
 
We will see less advances now that Trump is in there killing healthcare and the people that depend on it. He'll just tell you to go to the church and pray because science isn't real.

[Reply ]

    Re: Thanks to science!
    Posted on: 2017-10-15 16:49:18   By: Anonymous
     
    Non sequitur.

    [Reply ]

      Re: Thanks to science!
      Posted on: 2017-10-15 19:53:32   By: Anonymous
       
      I’m pro-sequiter

      [Reply ]

        Re: Thanks to science!
        Posted on: 2017-10-15 22:08:29   By: Anonymous
         
        Be-quite

        [Reply ]

No Subject
Posted on: 2017-10-16 07:46:36   By: Anonymous
 
Let's keep this away from big pharm and the hungry GOP profiteers.

[Reply ]

    Re:
    Posted on: 2017-10-16 07:56:16   By: Anonymous
     
    What's the likelihood of that? Merck or one of them will fund more studies in exchange for the initial patent and only those with access to truly good medical care will benefit. At least for the ten or so years that the patent rights run. It's a wonderful thought all the same.


    [Reply ]

      Re:
      Posted on: 2017-10-16 12:32:33   By: Anonymous
       
      Developing a major drug now costs about $ 1 billion (with a B). A pretty large percentage of them fail, meaning there is never any income from them. If Merck and Pfizer and the rest didn't get to make a big profit on their successes, then there would be no one left to take the risks of drug development.

      That said, here are two places that I think do deserve criticism and maybe more regulation:

      1. When Merck or whoever does get a new, terrific drug approved they sell it in the US for much higher prices than they sell it for in the EU or Canada or Mexico. That forces US patients (or their insurance) to cover an unfairly large share of the cost of drug development. Prices should be the same in all 1st world countries. One step toward that would be to let Medicare negotiate drug prices.

      2. Drug discovery is expensive and genuinely new drugs need to be expensive. But generic drugs are not expensive to develop and they should be much cheaper. Sometimes they are, but sometimes prices are kept high because...well, because the generic manufacturers can do that and are sometimes encouraged to do it by the original developer (We all make more money...wink, wink). Competition is supposed to prevent this sort of thing, but for reasonable business reasons there is often only a single generic maker. A duopoly is not much better than a monopoly from a patient's point of view. I'm not sure how to fix this. Maybe an excess profits tax, although it would be hard to enforce.

      The real problem, of course, is there is no limit on what big pharma can spend on lobbyists and PAC donations. So Congress is not going to fix these problems until that changes. And thanks to the Citizens United decision of SCOTUS, that is not going to change without a Constitutional amendment. So it's not going to change.

      [Reply ]


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