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PCLX-001 is similar drug in clinical trial that target cancerous cells but spares the healthy one, it's not the same target as the one in the article but I think (I'm not a biologist) that it's a similar mechanism. They even have a test to know beforehand if it's going to be effective in a particular cancer. It's developed by a company named Pacylex.
Here's the link to the clinical trial
https://clinicaltrials.gov/ct2/show/NCT04836195?term=pclx-00...
Edit: removed a duplicated word
MTDH is important for most major human cancers, not important for normal cells, and it can be eliminated with no obvious side effects
I'm not fully buying that.
If you look at "Function" on Wikipedia, it seems to have some important roles, including angiogenesis (which is still important outside of cancer). It's not like evolution would select for something that is useless outside of helping cancer.
I'd be curious what the side effects are in humans. How can it be claimed that it can be eliminated with "no obvious side effects" when they are still years away from human trials?
https://en.wikipedia.org/wiki/MTDH
Disclaimer: Iām not in these fields but I am curious enough about how the mechanisms work at a high level that I feel confident about the rest of this post.
Two things to keep in mind:
1. Biology has never selected genes to maximize longevity, only to maximize healthy breeding. There are very likely tons of genes that make sense as a growing child but are harmful at a later age, e.g. a post menopause/vasectomy adult does not need the genes to create gametes but those same genes may be causing cancerous issues for some.
2. Gene therapy (at least CRISPR-Cas9 like things) are in theory reversible[0]. Diagnose the cancer. Delete the notable gene or just make a point mutation to disable it. Treat/wait the cancer into remission. Re-add the notable gene or re-enable it with a point mutation. Hopefully such a strategy would minimize any long term effects and eliminate the cancer.
[0] There may be cases where a bio-engineer could design an effective yet irreversible edit. However, that seems like it would require serious effort and I doubt it would have enough value to be approved by the FDA for use.
> Biology has never selected genes to maximize longevity, only to maximize healthy breeding.
That is assumption which is hard to validate. There is a case for longevity as children with longer living dedicated parents in the context of abundant resources will out survive those that are ditched by their parents.
> Delete the notable gene or just make a point mutation to disable it.
The article say that effect is the same with deletion and drug in mice. Why would you delete the gene when you can temporally prevent its function ?
> Delete the notable gene or just make a point mutation to disable it. Treat/wait the cancer into remission.
Yet nobody did nothing remotely close in humans, even for stuff that looks like highly beneficial in all contexts such as GULO gene.
I agree with your sentiment, but this condition...
> in the context of abundant resources
...has only been true for a tiny number of generations and so likely has not had a large evolutionary influence.
Abundant is probably too strong word.
Obviously the system can't work to the extreme due to the limited resources, but there is lot of possible contexts that can last for a long time.
Also, evolution isn't "complete". It's not done optimising. And sometimes, some things evolve and there just isn't enough evolutionary pressure to remove stuff that does't hurt. Men have nipples.
> Men have nipples.
Just sayin', that has little to do with "remove stuff that does't hurt", but the fact that there is very little difference between men and women besides sex steroid levels. In particular, women do not have any genes men don't. The Y-chromosome adds the tiniest modification to gonadal development in embryos and that's it; androgens do the rest. With the right hormone levels, men can develop fully functional breasts; without estrogens, women don't.
Cancer definitely hurts.
>>> 1. Biology has never selected genes to maximize longevity, only to maximize healthy breeding. There are very likely tons of genes that make sense as a growing child but are harmful at a later age, e.g. a post menopause/vasectomy adult does not need the genes to create gametes but those same genes may be causing cancerous issues for some.
This is being debated, in the sense that there is a relationship between longevity and breeding. How ? For a human to be able to have kids every 2-3 years - instead of 6-7 in apes - older individuals have to be healthy enough to bring a calorie surplus to the mothers.
Adding to point 2, gene therapyās effects seem to wear off after a couple of years.
The MTDH gene clearly has _some_ utility in the human body. We know that because natural human knockouts are under-represented in the population. The Gnomad project has sequenced very many people's DNA, and they have been able to work out a formula for how many loss-of-function mutations they would expect to see in a gene (which mainly depends on the size of the gene). For the MTDH gene [0] they would expect to see on average 30.5 LoF mutations, but they only actually see 7. This is reasonably strong evidence that knockouts of this gene are selected against - that is, having two working copies of this gene conveys some advantage of some kind.
Knocking out the gene and gaining protection from cancer is likely a bigger advantage than whatever you lose, especially if you currently have cancer. Also, the proposed drug doesn't knock out the gene - it just prevents the protein from performing one of its interactions. Side effects are likely to take a while to work out, but if they're milder than the side effects of chemotherapy (which isn't hard) then that's a win.
The other thing I would like to point out is that humans and mice differ. It looks like most of the work they have done so far has been in mice. Knockout of this gene in mice doesn't seem to cause any ill effects. Working out whether the same is true in humans is a long and very careful process.
[0]
https://gnomad.broadinstitute.org/gene/ENSG00000147649?datas...
Angiogenesis is going to be important in wound healing, I suppose, but compared to the current side effects of chemo this seems relatively minor.
I agree that "no obvious side effects" seems excessive if you interpret that as the expected result in humans. Still, on paper this looks much more specific that anything we have.
Thats a pretty important consideration here. If I was looking at chemotherapy & its side effects vs alternatives... the side effect list from these angiogenesis inhibitors looks a lot more focused, the sort of thing you can develop a focused regime around the monitoring and management of.
Considering that people still get prescribed Thalidomide to limit angiogenesis as a cancer treatment, and we know about its side effects (lets ignore birth defects for now), I see no particular difference with this drug.
You're challenging someone with 15 years experience studying this particular gene... by quoting Wikipedia?
That someone has skin in the game and a reason to manipulate other peoples understanding for his own gain though. Not saying he is, but I dont think the original comment was unjustified
You acting like posters on HN don't have skin in the game as they try to appear smart in front of their peers.
āDo your own researchā
Ah the classic appeal-to-authority-fallacy ...
https://yourlogicalfallacyis.com/appeal-to-authority
From the link you posted:
> It's important to note that this fallacy should not be used to dismiss the claims of experts, or scientific consensus. Appeals to authority are not valid arguments, but nor is it reasonable to disregard the claims of experts who have a demonstrated depth of knowledge unless one has a similar level of understanding and/or access to empirical evidence.
At no point have I dismissed any expert.
Thanks for the quote tho, whats your point?
The point is quite clear. It's not an appeal to authority. Experts are generally more qualified to express opinions on their topic of expertise, but this doesn't make them immune from criticism. It does, however, make it a bit harder to call their view into question, and calls for a more sophisticated approach, usually by referring to problems with their evidence or absence of consensus.
Suppose an expert in a field has offered an opinion on their topic of expertise. You criticise that view based on unreliable evidence. I point out to you that your evidence is unreliable, and that the expert's view should be preferred due to its higher reliability. It's no answer for you to invoke the appeal to authority fallacy. You need to show that your evidence really is reliable, or why it's wrong to characterise your evidence as unreliable.
Suppose on the other hand that an expert in a particular field offers a view outside of mainstream consensus. I say that his view should be accepted. You say his view is not mainstream consensus. I say that he's an expert so he must be right. This is an appeal to authority.
I think it's important to distinguish the authority of expertise from the authority of power.
This isn't an appeal to authority, though. Also note there's a fallacy on there about using fallacies to discredit someone.
> It's not like evolution would select for something that is useless outside of helping cancer.
Cancers often have genetic basis so in a sense evolution has already selected for it in some people or at least not selected against it.
IANAdoctor/biologist but i assume diseases that tend to strike after child bearing age have less negative selection pressure than other diseases.
> IANAdoctor/biologist but i assume diseases that tend to strike after child bearing age have less negative selection pressure than other diseases.
It gets even better: there is selective pressure for adults that have borne children to die so that their children can procreate. First noted in pea plants that send a chemical signal to kill themselves up from the pod, can be extended to animals in things like cancer rates.
Except that humans are not pea plants and having grandparents play an active role in child rearing significantly improves the survival odds for their grandchildren (who carry a quarter of their genes).
Humans arenāt peas. Pea grandparents donāt help out in child rearing but human grandparents do. There is no indication that humans face selective pressure to die early.
>There is no indication that humans face selective pressure to die early.
While I do agree that pea plants are different, human grandparents may help in child rearing, but they may also consume time and energy for care.
We're social animals that would not kill our own grandparents for having more food/time available. But nature might find it's useful for procreation if they don't live too long.
Elderly care is a huge time/energy sink. And longevity makes the input/output unfavorable in a lot of cases.
If you're in an environment like our ancestors where food was most of the time scarce, then that adds weight to this equation.
There is evidence that earlier death can help animals, so it is appropriate to extend it to all animals barring evidence to the contrary.
Long lived, already procreated animals limit the amount of evolution that can take place by drawing out the time between procreation events. So if you have 2 species, one which dies earlier but has more generations, you expect them to outcompete a longer lived species.
I didnāt read the article fully but the parts of those two papers that are public and available to me (see Extended data Fig.4 comment at the bottom of the first paper), those do not talk about turning off a gene that encodes MTDH.
The paper is talking about a compound (two compound candidates) that inhibit binding of two proteins: AEG-1 (encoded by MTDH) and SND1, those compounds do that by binding to either AEG-1ās or SND1ās site where otherwise SND or AEG-1 would have bind, and they likely do this with stronger bond than SND1 and AEG1 would have had.
So in short, this compound does not leave you without some vital protein but disrupt formation of some bonds with SND1 protein.
No obvious side effects in mice with knockout gene and using the drug.
The drug doesn't disable the gene but make the protein unable to do its function by preventing the binding with another protein. If it can make cancer chronic disease, any side effects it may have will probably be less important then death.
A lot of proteins are involved in angiogenesis. Not to say it isn't important, but the body has many redundancies to make sure small errors don't break the whole system. That alone doesn't necessarily mean much, hence the MTDH knock out mice(model mice with the MTDH gene turned off) shows no obvious side effects. I suppose we'll see with time whether that holds up when applied in practice.
Thereās also a lot of redundancy in biology. A protein could be essential for cancers and non-essential for healthy cells. Thatās the holy grail.
Entirely possible that while itās involved in angiogenesis, itās not a critical component of that process, and angiogenesis can continue just fine without it.
The statement ānot important for normal cellsā doesnāt mean it serves zero purpose outside of cancer, all it means is that itās not critical for body functions.
I know nothing about biology, medicine or evolution, but I don't think that's how it works. Lots of people inherit and pass on all kinds of bad genes that do terrible things to them, even kill them. And for such people, switching them off would be better pretty much irrespective of any side effects. (to the degree there even are any side effects at all)
Itās one thing for a ābadā gene to stick around for a few generations or even spread through a species. Itās wildly different for a ābadā gene to be shared by species whoās common ancestor was 60+ million years ago. On that timescale anything conserved is doing something useful.
_Useful_, yes, but for whom? Not necessarily the individual. The ultimate goal of the genes is to propagate themselves, possibly in another body.
In the contemporary research of aging, the hypothesis that "aging is actually at least partly a programmed process and some genes useful in youth may turn against us later" is taken seriously. There seems to be an intriguing negative correlation between age of sexual maturity and lifespan in mammalian species.
> some genes useful in youth may turn against us later
Thatās very much still useful for the individual, from an evolutionary standpoint. Of course finding out what something does isnāt the same as finding it needed for you. People get vasectomies which are hardly something evolution is going to do.
The extreme prevalence of testicular and breast cancer are likely the kind of trade offs that modern individuals donāt want, but they are a likely a consequence of some useful feature for our ancestors evolutionary environment.
> I know nothing about biology, medicine or evolution, but
well, by all means, don't let that stop you
this site is FULL of people who make wildly unqualified, unsourced, incorrect claims and passing them off as fact
but you have to have a dig at the one guy who clearly and openly admits they don't know anything before continuing with "but I _think_"
wow
Might be important for sustained metabolism, but it might be eliminated for long enough to starve the disease.
I donāt know, but I do know the reality provides more combinations than I can imagine, especially when presented with binary and mutually exclusive scenarios.
Here is the research:
Small-molecule inhibitors that disrupt the MTDHāSND1 complex suppress breast cancer progression and metastasis
https://www.nature.com/articles/s43018-021-00279-5
Pharmacological disruption of the MTDHāSND1 complex enhances tumor antigen presentation and synergizes with anti-PD-1 therapy in metastatic breast cancer
https://www.nature.com/articles/s43018-021-00280-y
Metastatic research really needs more funding. It's the true killing mechanism of cancer, and when this can be controlled, metastatic cancer can be classified as a chronic condition, not a terminal one.
What takes years to develop for the human trials to start?
Is it about optimizing the delivery system, or finding the right targets to test on in bigger animals first?
There are so many people closecto dying in cancer, that finding volunteers for a Phase 1 test should be easy.
I have a friend who about 15 years ago was told he was going to die from melanoma in about a year.
Within that first year he was put on a trial that added another 2 or so years to his life. Then during that time another experimental treatment was created and tested on him and that gave him another couple of years. A decade and a half later here we are, he still has cancer but his family (wife and two kids) has got to keep him around a while longer.
Heās been āpatient oneā on a number of studies, some have helped him extend his life expectancy, others have done nothing. Sometimes he has the mental and physical energy to start a trial and other times he does not.
The cancer has never gone away, and there have been so many moments of false hope that Iām never really sure where he sits mentally anymore (he really doesnāt want to talk about cancer when weāre together and I donāt think anyone can blame him) but I know heās grateful for the chance to add more time onto his life when the experimental treatments are available.
The thing about trials is that there's a reasonable chance the patient ends up in the control/placebo group, which is something to think about when signing up for miracle. It could help explain some of the "done nothing" studies in your friend's journey.
A good friend of mine signed up for a trial as an alternative treatment for her aggressive breast cancer, everyone's hopes went up (trials tend to have that effect on people) but "nothing happened". She passed away 6 months after the trial started without knowing if a placebo was used. It's painful anecdata, but the few people I know that got into cancer studies as an alternative to their regular treatment, none ever had the study knowingly influence their outcome. Yet, in every case, the study was the one-hundred-percent animic lifeboat to grab on to.
Participating in a trial is about helping science just as, or more than, it is about helping yourself.
Yeah he always took some pride in being that early patient in a study.
As an aside, Iāll have to be careful here because I think I might be confusing some of the trials he was a part of with actual treatments he received. Itās been a big mix of throwing a lot of different things at the wall.
Yeah my friend has been doing that for about half as long. It still sucks. Some of the modern, immune-based therapies don't make your hair fall out, but they still can wreck your digestive tract, thyroid, and adrenals(in my friend's case, permanently). There are surgeries as well, and getting slowly hacked up as they chase tumor after tumor isn't fun.
Still though, it's a better time to have cancer than ever I suppose.
Iām sorry your friend is in a similar position.
There was one treatment that they were going to trial my friend on that would give him another expected extension but basically make his digestive tract stop working so heād be pooping out of a tube into a bag the rest of his life but he declined, said it just wasnāt worth it.
There have been a couple times thatās been the call heās made and I appreciate why.
Good luck to your friend - sometimes it is not worth it, but the chances he has been taking and the suffering he has been going through in those trials where it is worth it is hopefully helping others in the future with the same disease.
Cancer sucks; why it is so hard for us to beat is so frustrating. need more research focused on this.
He is both fortunate and unfortunate. Must have a very difficult fifteen years.
Is that study a randomized controlled study? Was your friend in the control group or in the experimental group? What was the difference of the outcome in both groups?
It's very rare that everyone in the control group dies and everyone in the experimental group survives. Usually the result is mixed.
The problem is that medical doctors sometime make bad guess about how many years the person will survive. That's one of the reason to have a control group, so the error in the guess compensate.
For anyone reading, the control group for cancer trials is the best current treatment, thereās no placebo control.
Yep, standard of care is used in control groups. Also, there are trials in which people are moved from the control arm to the experimental treatment upon increase in tumor size, which allows participants to get a chance to actually trial the drug.
Vince DeVita said it was the main strategy in the 60s. Extend enough to find a new idea. Today things are standardized but if you fall out of the solution, you're given morphine and a bed. Which I find dreadful. Your friend life is a, pardon my french, interesting story.. because he managed to jump above deadlines but I can understand how spiritually damaging it is to always take your fate in your own hand every few years.
Good luck to him
The new immunotherapies should be tried if he hasn't done any yet.
Assuming you have found a drug that is safe and binds the target in the intended way (which itself can take years), you then have to manufacture it according to GMP standards. That takes at least a year and $1 million. Next, you have to run toxicity and pharmacokinetics (how the drug is absorbed and distributed in the body) in two different animal models. That takes 6-12 months and $1-2 million. Then you apply for permission to start phase I trials, and wait for the green light.
One reason RNA drugs are so exciting is that their manufacture is simple and can be standardized, cutting the GMP manufacturing step to a few weeks instead of a year or more. Small-molecule drugs are ābespokeā in that each needs its own, different, manufacturing process. In contrast, all RNA molecules are essentially chemically identical, differing only in the ordering of the nucleotides.
Need to make a drug out of the small molecule inhibitor. There is a medicinal chemistry process that takes quite a while (several years at times) to get to something you can actually give to people.
Then there is safety testing in animals. Then regulatory approval. Then starting the phase I trial. The trial might take a year or more. Then you need to show the drug works compared to some standard treatment, which in a phase 3 trial in breast cancer takes 3 years and many hundreds of patients at least. Longer if you want to show it prolongs overall survival. Then the drug needs to be approved.
There is also the matter of funding but there is a lot of money for early stage biotechs at the moment.
In my (unpopular) opinion trials for people with incurable cancer are quite predatory. You are supposed to participate to help science, not yourself. But in reality many people desperately cling to anything that gives them hope.
The article seems to suggest that they only just found a compound which will interfere with the gene's action. So up until now, there was nothing to test.
The 2014 result only showed that gene editing before birth might prevent cancers.
From the article:
"yet it doesnāt seem to be important for normal development"
Gene space is huge. My cancer is cured, but now I'm dying of mange. So that's why that mouse kept licking itself. Big ask for someone else. They have trouble getting blood thinners, statins and beta blockers right. And there's no genetics there. It's stuff people ate out in the woods for hundreds of thousands of years.
> There are so many people close to dying in cancer finding volunteers for a Phase 1 test should be easy
I take the opposite approach. These people have few days left. It's a time to make things nice. It can get much worse quick. Cancer, which can be managed, is nowhere near as bad as it can get.
Disease tends to hit all at once. It's really just dying. Cancer, strokes, heart attacks and infections all tend to gang up at once. The trial will kill these people no doubt. If you have a ticket out of the hospital, take it! Don't squander it trying to wash mud.
Also the patient pays a lot for clinical trials. Hundreds of thousands of dollars.
You seem to be getting downvoted. Not sure why.
I've had someone in the family who got cancer. It was basically how you said it would be. They lived their life to the fullest, not thinking about the untreatable cancer. Do whatever is fun and makes you happy.
At some point it got bad. No more living your life. There were bad moment. There were better moments. There were worse moments. I only saw it from afar until the very end. The last bit must have been hell for the closest family. It really is just dying. Slowly. Painfully. And all society and doctors try to do is to prolong the suffering.
I'm being unfair to some people. I do know the palliative care team did their best. All volunteer doctors. Power to them.
Agreed (except the part about the patient paying for clinical trials). After I got diagnosed with metastatic prostate cancer last year I was asked to participate in a immunotherapy trial. I declined as a wasn't about to spend the next two years (that could very well be my last) going to the hospital every three weeks to be poked and prodded.
Wait what? Trails aren't free to participants? That alone is going to majorly bias the results.
Here take this medicine, we are fairly confident it won't kill you. Here is your $100k bill. Oh? Can't afford that? No trial for you!
Trials are absolutely free for the participants. Insurance wonāt pay for non-FDA approved treatments and itās illegal to charge for them anyway.
Ancillary routine FDA approved testing that accompanies the trials may be billed to insurance in some cases? I donāt know about that. But a trial for a novel cancer treatment will be free, if not even include an honorarium of some kind to defray costs to the patient for participating.
Generally patients don't pay extra for clinical trials, although it's complicated. Their insurance usually pays for patient care costs, routine costs you'd have regardless of the trial. The trial usually pays for research costs, tests and stuff specifically due to the research.
https://www.mskcc.org/cancer-care/clinical-trials/frequently...
Acquiring endless regulatory approvals.
I don't mind that it takes a little proof to convince regulatory boards to approve medicines for Phase I trials, but these days Phase I trials are fairly quick to get (assuming you can sell the doctors and patients on it).
My guess for the delay is production process and delivery mechanisms. There are delivery mechanisms where the combinatory effects lead to some serious toxicity.
Plus, how long do mice live for? I'm sure they are still taking down observations and collecting data. The article submission may be to help with funding.
I wonder how much of our regulation around medicine is wasteful, vs regulation that came about in response to some sort of malfeasance.
Most of it is probably both.
I worked in medical devices, and that is correct. Much of the work I did in the QA dept would not have improved the product or safety, but some of it clearly did. Can't say for medicines, as they had a different set of regs from devices.
It is both. The last time we had very free experimentation (read: disregard for human life and suffering) we got the Nazis, the Tuskegee Syphilis Study, MKUltra, etc.. So institutions swung strongly in the opposite direction (the visible ones, at least), giving us Institutional Review Boards and such. The balance is impossible to get right either way, hence the need for Right to Try and so on.
āYou canāt find a drug target better than this: MTDH is important for most major human cancers, not important for normal cells, and it can be eliminated with no obvious side effects,ā said Kang.
"Because while itās important to show that mice born without MTDH are resistant to cancer, that doesnāt help patients, _whose genes canāt be rewritten_."
...yet
Wonder if we'll look back at this and think "how quaint".
Actually, we can: I think we already have working gene therapy for several diseases.
Just look at the current list on wikipedia:
https://en.wikipedia.org/wiki/Gene_therapy#Treatment_of_gene...
Huntington's is an invariably fatal disease, which is caused by the repetition of a single gene, which overexpresses a single protein. It's about as simple as genetics get. When we've cured that, I'll say we have working gene therapy.
As someone with some genetic diseases, itās feels unfortunate to be born too early
We donāt have a good enough delivery mechanism to get it to 99.99%+ of cells. So how well a gene therapy is really depends on how many of the cells need to be targeted.
For example, increasing muscle mass is beneficial even if it hits only 25% of cells. It can also be injected directly into each large muscle group. Or specifically targeted.
Meanwhile, trying to target pancreatic cancer is really hard given itās location, and depends on if the ābad proteinsā would be transported by blood to the pancreas anyways and/or if even 0.01% of cells creating the protein is enough to sustain the problem.
We don't have the capability to turn off a single gene in all living cells in a body. We have some applications of gene therapy, but they're very specific to the disease they're treating
Neo: āAre you trying to tell me that I can alter DNA?ā
Morpheus: āno Neo, Iām trying to tell you that when youāre ready you wonāt have toā
Altering the DNA is unnecessary if you can control the expression of genes or add additional genetic material later in the DNA->RNA->protein process. mRNA vaccines are already a great example of this. Another example might be the cystic fibrosis therapy Trikafta.
_octopuses and their relativesāthe cephalopodsāpractice a type of genetic alteration called RNA editing thatās very rare in the rest of the animal kingdom. They use it to fine-tune the information encoded by their genes without altering the genes themselves. And they do so extensively, to a far greater degree than any other animal group._
https://www.theatlantic.com/science/archive/2017/04/octopuse...
Disclaimer: Iām not a scientist, but I want to be.
For things like cancer cells which from a cell surface perspective, can look a lot like healthy cells, I donāt know how one only modifies DNA/RNA expression in only cancer cells. It would have to be all cells with maybe some cellular diagnosis logic in the DNA/RNA itself. Even then cancer evolves. It would have to done multiple times with something like cell descendents information.
Targeting doesnāt have to occur at the cell surface does it?
Perhaps something like introducing tumour suppressor genes to every cell. Theyāll have no effect on healthy cells yet detect ābadnessā in cancerous cells and terminate them.
Nearly a Trifakta
Epigenetics are very easy to alter with peptides
Nicely written, well explained and letās hope that the MTDH will help in suppressing cancer. Not yet available, but their hard work will soon pay out.
āI hope weāll be ready for clinical trials in human patients in two to three years,ā
"MTDH was amplified ā meaning it produced MTDH proteins at abnormally high levels compared to normal cells ā in 30 to 40% of tumor samples"
That doesn't sound great, unless the 30-40% was only and all of the metastatic type.
My cynicism leads me to think if the news was that good, they would clearly state it.
Also, I read this:
"for some, maybe five, 10, 15, 20 years later, theyāll have a recurrence, often as metastatic relapse"
...and think, so how long does it take to prove that you've prevented this, huh?
Curing 30 to 40% of a population is still a big win.
Does it even mean this though?
If youāve attacked 30%-40% of the tumours in each patient, no-one is cured.
Yes, this is what it means. Why does everybody here assume everyone outside the software profession is an idiot. Obviously if it only attacked 30% of tumor cells it would be useless. I'm not going to go over the physiology of cancer here, but basically yes targeted therapy works because of the common progeny of cancer cells.
>Why does everybody here assume everyone outside the software profession is an idiot
Why does everybody here assume everyone here is a SV software engineer, except for them? You could be insulting someone in high school.
Cancer affects people from every walk of life, so there's a good chance a random non-medical person in a thread like this has some experience that they are drawing on, like seeing a family member die up close and interacting with oncologists.
>Obviously if it only attacked 30% of tumor cells it would be useless
I think _both_ of you made up things that weren't actually stated. It didn't say that 30-40% would be cured _or_ that 30-40% of the tumors would be eliminated.
Yeah I really don't know. It was a genuine question.
So what is, or are, the "small-molecule inhibitors"? (I don't have access to the full texts of the papers.)
Also, what makes them confident these inhibitors "suppress breast cancer progression and metastasis"? Does this mean only in the mouse model? Because the original article says "will be ready for human trials in a few years".
A small molecule is exactly what it says on the tin: small compounds. Small enough that they can pass through cell membranes.
Inhibitors block some biological pathway, which in general could be any number of things.
In this case the drug blocks a specific protein that we believe cancer cells specifically need, meaning the cancer cells might fail faster than the rest of your body if we inhibit it.
So, not a scientist here, and I know this is not their research direction, but would a gene therapy be possible using something like CRISPR to just "edit out" the MTDH gene? I know we are kind of in early days for that..
Fascinating that they have to physically screen individual molecules one at a time to see if they can bind with a specific protein. Even at a Princeton lab, it took years. Are there other institutions/companies working in this space?
If we can get some new tools for the fight against cancer in the next few decades, this will be just so huge. It feels like we're right on the edge of this possibility. Now if we can just avoid the red tape along the way.
The Chinese military are spending vast vast sums on gene therapy.
They call it precision medicine.
ctrl+f >in mice
...and human tissue.
>'in a few years'
No. You're reading it wrong.
It says: "which he can NOW disable, in mice and human tissue, with a targeted experimental treatment that will be ready for human trials in a few years."
They have disabled it in human tissue NOW and human trials will be in a few years.
Weāll all be well dead before this becomes available to us.