Princeton Team Disables Long-Targeted Gene Behind Spread of Major Cancers (newatlas.com) 55
An anonymous reader writes: The mysterious ways cancer spreads through the body, a process known as metastasis, is what can make it such a difficult enemy to keep at bay. Researchers at Princeton University working in this area have been tugging at a particular thread for more than 15 years, focusing on a single gene central to the ability of most major cancers to metastasize. They've now discovered what they describe as a "silver bullet" in the form of a compound that can disable this gene in mice and human tissue, with clinical trials possibly not too far away.
This discovery has its roots in 2004 research in which Princeton scientists identified a gene implicated in metastatic breast cancer, called metadherin, or MTDH. A 2009 paper by cancer biologist Yibin Kang then showed the gene was amplified and produced abnormally high levels of MTDH proteins in around a third of breast cancer tumors, and was central to not just the process of metastasis, but also the resistance of those tumors to chemotherapy. Subsequent research continued to shed light on the importance of the MTDH gene, demonstrating how it is critical for cancer to flourish and metastasize. Mice engineered to lack the gene grew normally, and those that did get breast cancer featured far fewer tumors -- and those tumors that did form didn't metastasize. This was then found to be true of prostate cancer, lung cancer, colorectal cancer, liver cancer and many other cancers.
The crystal structure of MTDH shows the protein has a pair of protrusions likened to fingers, which interlock with two holes in the surface of another protein called SND1. This is "like two fingers sticking into the holes of a bowling ball," according to Kang, and the scientists suspected if this intimate connection could be broken, it could go a long way to dampening the harmful effects of MTDH. "We knew from the crystal structure what the shape of the keyhole was, so we kept looking until we found the key," Kang says. The team spent two years screening for the right molecules to fill these holes without any great success, until they landed on what they say is a "silver bullet." The resulting compound plugs these voids and prevents the proteins from interlocking, with profound anti-cancer effects that resemble those seen in the MTDH-deficient mice from their earlier work. "The scientists say that MTDH assists cancer in two primary ways, by helping tumors endure the stresses of chemotherapy and by silencing the alarm that organs normally sound when a tumor invades them," adds New Atlas. "By interlocking with the SND1 protein, it prevents the immune system from recognizing the danger signals normally generated by cancerous cells, and therefore stops it from attacking them. The team is now working to refine the compound, hoping to improve its effectiveness in disrupting the connection between MTDH and SND1 and lower the required dosage. [T]hey hope to be ready for clinical trials on human patients in two to three years."
The research has been published across two papers in the journal Nature Cancer.
This discovery has its roots in 2004 research in which Princeton scientists identified a gene implicated in metastatic breast cancer, called metadherin, or MTDH. A 2009 paper by cancer biologist Yibin Kang then showed the gene was amplified and produced abnormally high levels of MTDH proteins in around a third of breast cancer tumors, and was central to not just the process of metastasis, but also the resistance of those tumors to chemotherapy. Subsequent research continued to shed light on the importance of the MTDH gene, demonstrating how it is critical for cancer to flourish and metastasize. Mice engineered to lack the gene grew normally, and those that did get breast cancer featured far fewer tumors -- and those tumors that did form didn't metastasize. This was then found to be true of prostate cancer, lung cancer, colorectal cancer, liver cancer and many other cancers.
The crystal structure of MTDH shows the protein has a pair of protrusions likened to fingers, which interlock with two holes in the surface of another protein called SND1. This is "like two fingers sticking into the holes of a bowling ball," according to Kang, and the scientists suspected if this intimate connection could be broken, it could go a long way to dampening the harmful effects of MTDH. "We knew from the crystal structure what the shape of the keyhole was, so we kept looking until we found the key," Kang says. The team spent two years screening for the right molecules to fill these holes without any great success, until they landed on what they say is a "silver bullet." The resulting compound plugs these voids and prevents the proteins from interlocking, with profound anti-cancer effects that resemble those seen in the MTDH-deficient mice from their earlier work. "The scientists say that MTDH assists cancer in two primary ways, by helping tumors endure the stresses of chemotherapy and by silencing the alarm that organs normally sound when a tumor invades them," adds New Atlas. "By interlocking with the SND1 protein, it prevents the immune system from recognizing the danger signals normally generated by cancerous cells, and therefore stops it from attacking them. The team is now working to refine the compound, hoping to improve its effectiveness in disrupting the connection between MTDH and SND1 and lower the required dosage. [T]hey hope to be ready for clinical trials on human patients in two to three years."
The research has been published across two papers in the journal Nature Cancer.
metastasis? (Score:2, Funny)
Isn't that what happened to FacePlant?
Re:Long-Term Cancers from Covid "Vaccines" (Score:4, Insightful)
Re: (Score:3, Interesting)
In response to an AC's provocation:
Can we just focus on the long-term effects of the "vaccines" and get them out of the picture? All y'all with the clot shot are going to die from it.
A second AC plaintively inquired:
Why do you believe these things? There's nothing behind these silly notions. Your gullibility is hurting you.
He doesn't believe "these things," any more than you do. He's straight-up trolling in a successful attempt to soak up downmods, so that those points are not available to upmod reasoned, intelligently-argued, left-of-center posts.
It's a tactic that's endemic to /.'s broken moderation system, specifically because the combination of posting as AC (which costs the poster no karma) to create this kind of honeypot for well-intentioned moderators to waste their points on, and the e
Re: Long-Term Cancers from Covid "Vaccines" (Score:1)
Re: (Score:2)
Why do you believe these things? There's nothing behind these silly notions. Your gullibility is hurting you.
SHHH! If you talk him into getting vaccinated, we lose the chance to raise, however slightly, the IQ of the population.
Re: (Score:3)
I can say without a doubt that everyone who uses slashdot will die in the next 80 years.
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I wouldn't go that far.
Average life expectancy right now is around 80. Which likely means reaching 100 isn't out of reach for a young-ish human today.
Now, whether a "young-ish human" is likely to read /. is a whole 'nuther question. But I don't consider it impossible....
credit where credit is due ? (Score:5, Insightful)
The magazine rack at my bookstore is filled with the smiling faces of millionaire movie stars, sports stars, rap singers and others of doubtful accomplishment. These Princeton scientists belong there too, but instead they are nameless until one gets a Nobel prize.
Re:credit where credit is due ? (Score:5, Insightful)
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Don't forget the graveyard keepers. They won't like it.
Re: (Score:2)
Pricey surgeons who make a mint cutting out cancers will need another way to make their boat payments
Re:credit where credit is due ? (Score:4, Insightful)
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So does every other company in existence, for your entire income.
Re: credit where credit is due ? (Score:2)
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So does every other company in existence, for your entire income.
I can avoid giving my money to corporation I don't like by not buying their products. Please tell me more on how can I not pay taxes to a government I dislike.
Re: (Score:2)
Move to where there's a government you do like?
Chances are, the governments you like (ie, the ones that keep the roads from falling apart, criminality in check, etc) are pretty good at collecting taxes and generally collect a fair amount.
The ones you don't like may not be good at collecting taxes or will, for a small fee, allow you to underpay or not pay. But then you'll have to live in some kind of gated compound and provide for yourself in ways that is difficult in such an environment.
Re: (Score:2)
I suppose they could move to a low-tax republic and then spend their money on security forces...
Re:credit where credit is due ? (Score:5, Insightful)
So let us blame the government and taxes.
Great thinking buddy. Did you ever think if government of the people, by the people, for the people actually could try to stop capitalism from grabbing the society by its balls and squeezing it hard?
Act 1: Government should be small enough to be drowned in a bath tub.
Act 2: Corporations are people, and they get all the rights including free speech and religious beliefs.
Act 3: Money is speech.
Act 4: Corporations drown the government in a bathtub.
And you are still railing about big govt and taxes? In the very same sentence where you correctly fix the blame on unrestrained capitalism?
Re:credit where credit is due ? (Score:4, Funny)
Like the old saying goes I'll believe corporations are people when Texas executes one.
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Like the old saying goes I'll believe corporations are people when Texas executes one.
Please point me to a corporation that has married someone. After all if corporations have ALL the rights of people, surely one must have exercised the right to marry?
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In context of a corporation, I think that merger == marry
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Capitalism makes retirement fiscally impossible.
So let us blame the government and taxes.
Great thinking buddy. Did you ever think if government of the people, by the people, for the people actually could try to stop capitalism from grabbing the society by its balls and squeezing it hard?
Act 1: Government should be small enough to be drowned in a bath tub.
Act 2: Corporations are people, and they get all the rights including free speech and religious beliefs.
Act 3: Money is speech.
Act 4: Corporations drown the government in a bathtub.
And you are still railing about big govt and taxes? In the very same sentence where you correctly fix the blame on unrestrained capitalism?
Please tell me, how exactly "significant life extension screws up retirement system" problem unique to capitalism? Ah, of course, in a state-run retirement fund the govt just throws more taxpayer money at the problem. Forget I asked.
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I asked for enough powers for the government to regulate capitalism. The rights granted to us, nay recognized as existing by our Constitution, is for flesh and blood citizens. Corporations are NOT people. People should have higher rights than corporations. People are not created by a 25 $ filing fee with the department of commerce. People can not say, "I will accept all good things coming to be but not the liabilities". Corporations can not be jailed for criminal conduct. As such they do not deserve the same rights as ones who could be jailed or executed.
Did I ask for a state-run retirement system?
Oh sorry, you perfectly knew what I was asking. Suggesting a state-run retirement system as the alternative is the straw-man you carefully constructed to tear down and claim chest-thumping victory.
Forget I asked.
Ah, forgive me for thinking you were trying to stay at least vaguely on topic. Corporation-persons, indeed, and on-topic much. Please show me on a doll where the evil corporation-person has touched you.
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As they say in Culture Contact units, poverty is the sure sign that capitalism is being used economically
We need to continue to progress to a point where cost of production is so low (enabled by machine production) that humans can live well without money
And also a reflection of modern science (Score:4, Insightful)
Not only is credit often given way too late, the cult around specific persons does not reflect at all modern scientific practice. Just look at the article:
About 20 scientists working hard for years on a project together based on a 15 year old idea. And the 50 citations won't even cover all the necessary requirements to get this off the ground. And with an increase in complexity this trajectory spans beyond science.
Unfortunately (Score:5, Insightful)
Unfortunately for slashdot users, living forever would still require regular exercise and a balanced diet.
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Actually it's more about genes, rather than diet and exercise. Plenty of 100+ year olds said their key to longevity was smoking and drinking, in interviews.
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Fixed it for you.
This discovery could actually be a curse. The medicine will keep the body alive. Probably the brain alive enough to be aware of the miserable state the body is in. But all sorts of cancers growing without metastasizing, all organs weakened so much they could barely keep the body alive with the help of medicines...
I remember a documentary about
Re:Unfortunately (Score:4, Informative)
Re:Unfortunately (Score:5, Insightful)
A cancer that doesn't metastasize can just be removed. But even without cancer the body will continue to decay.
I have a pair of grandparents in their upper 90s. They are mentally healthy/agile and have no cancer, but their bodies are on the way out nonetheless. I could write pages about their various maladies, how much medical care they need both constantly and in frequent crises, and how things get worse and worse from year to year. We could eliminate cancer and that would be great, but I don't know where you would even start with the kind of gradual degradation that happens to even "healthy" people past a certain age.
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Yeh Ive been caring for my mid 90’s parents for 5 years now, had to watch my Mum die of dementia, and my Dad now bedridden in a Nursing home, I dont want to live that long. Quality of life after 85 really drops.
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While all of that is true, now, there are lots of anti-aging treatment possibilities that can't be explored because of their potential to cause cancer. We know how to make cells live longer, there has been good work even in rejuvenating cells, but cells that don't die are called cancer. Solve that, and a lot of life-extending possibilities open up.
Also reenables immune sys attack on initial tumor. (Score:5, Insightful)
This discovery could actually be a curse. The medicine will keep the body alive.... But all sorts of cancers growing without metastasizing,
Read a little deeper. The protein does two things:
1: Enables metastasis.
2: Disables a signaling system that normally activates the immune system to attack on, not just the baby tumors, but also the "mother tumor".
So the drug, or the drug in combo with other chemotherapy and/or (when possible) surgery for the initial tumor, is expected to result in the elimination of all of the cancer being treated (as well as others just getting started).
What's nice about this target is that it doesn't appear to have any NORMAL function to be disrupted, at least in mice. Knocking out the gene for it produces normal mice. So it's apparently (currently) JUST a cancer gene - genetic junk, such as a viral remnant, that, when enabled by a cancer's genetic/gene-regulatory noise, "improves" it with additional pathological capabilities.
Also: Maybe helps with other "old-age" illnesses (Score:3)
What's nice about this target is that it doesn't appear to have any NORMAL function to be disrupted, at least in mice. Knocking out the gene for it produces normal mice. So it's apparently (currently) JUST a cancer gene - genetic junk, such as a viral remnant, that, when enabled by a cancer's genetic/gene-regulatory noise, "improves" it with additional pathological capabilities.
And...
all organs weakened so much they could barely keep the body alive with the help of medicines...
Perhaps some of those other
How to solve problems (Score:2)
This discovery could actually be a curse. The medicine will keep the body alive. Probably the brain alive enough to be aware of the miserable state the body is in. But all sorts of cancers growing without metastasizing, all organs weakened so much they could barely keep the body alive with the help of medicines...
Sounds like a good application for an mRNA treatment: disable the MTDH gene in a way that wears off in 6 months while treating existing cancers.
That was just off the top, I'm sure people will come up with other solutions.
The way to solve problems is to find actions that put you closer to the solution. If an action makes a huge leap towards - but not exactly on - the solution, then you can look for subsequent smaller steps that get you even closer.
In this case finding the first big leap was really hard. Mayb
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This discovery could actually be a curse. The medicine will keep the body alive. Probably the brain alive enough to be aware of the miserable state the body is in. But all sorts of cancers growing without metastasizing, all organs weakened so much they could barely keep the body alive with the help of medicines...
I can understand the fear of living long enough to lose yourself from dementia or similar ailments.
However, cancer affects people of all ages, and this breakthrough could help *children* and many others live fuller, more productive lives. I just watched a family member die from a metastasized cancer, found after the organ which originally developed the cancer was removed. We could have had decades more with him, instead we got two months. This is phenomenally good news.
Cancer is the curse.
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Fixed it for you.
You didn't fix anything, you provided your less-accurate, magical-thinking version.
You should consider being more confident in your own agency. You don't have to try to displace somebody else in order to express your own idea. Maybe some pills for the ED would help?
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Even if you eliminated all disease and halted the ageing process very few people would live to be 1000. TL;DR there are many ways to die from trauma and over time you move from random events to stochastic and your dead. It's like being over ~80, where the age specific death rate has plateaued and it is just a numbers game from there on in.
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Yeah but this could possibly add 20 years average, and opens up the field of cellular rejuvenation; currently held back by cancer fears.
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Worse than all that, manifesto quality is in the gutter.
In the Old Days, crazy people could manage something insightful at the core of their rant, and then they'd fill it out with CIA space aliens.
anyone with gene already disabled? (Score:2)
So, are there people with this gene already naturally disabled? Do they actually not get cancer as much?
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I can't find information about humans with a fully defective MTDH genes, but there are mutants which have higher transcriptional activity. They are susceptible to migraine headaches. https://thejournalofheadachean... [biomedcentral.com]
Humans are a lot different from mice, so just because MTDH-knockout mice were ok, doesn't mean MTDH isn't essential for us.
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Reading your link, it seems this might also treat some cases of cluster headaches that are caused by increased MTDH due a nearby defective gene. I didn't see anything in it about defective MTDH genes, though, just evidence of additional harmful effects of MTDH.
Still no cure for cancer... (Score:2)
Still no cure for cancer...
Damn, we may not be able to use that line anymore in the near future. Maybe we'll have to change it around like the Seinfeld joke about putting a man on the moon...
How is it that we can manage to find a cure for cancer, but we can't fix tiny problem X?