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Anti-diarrhoea drug drives cancer cells to cell death

aktuelles.uni-frankfurt.de

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Re: Anti-diarrhoea drug drives cancer cells to cell death

#51

Post by billiam »

wittyreference wrote: post #9
xwdv wrote: post #4

How does it not also drive regular cells to death?

I don't know if chronic opioid exposure drives other cells to death. It certainly does cause some neuronal death, which we've already established with other opioids, also using the ATF4 mechanism. The tumor in this paper is a brain tumor. AKA, drug belonging to [drug class] that kills [neuronal tissue] will also kill [bad neuronal tissue] through same mechanism as [general drug class]. The key question is "if putting…

>The key question is "if putting a shit-ton of opioids (which already cross into the brain) in cancer patients doesn't already meaningfully treat this condition, why do we imagine that delivering the same class of drug past the blood-brain barrier suddenly will?"

It appears that as they say now that they have identified the specific mechanism of cell death that can start looking at ways to target the tumor cells without flooding the rest of the brain with loperamide or other opiates. It will be a good trick but better than the other (non) options for glioblastoma.

Re: Anti-diarrhoea drug drives cancer cells to cell death

#52

Post by adamredwoods »

Dumblydorr wrote: post #20

There is incredible potential out there, potentially dozens of useful treatments that are safe and cheap, and all we have to do is repurpose them. Consider that new drugs cost 1 to 2 billion to come to market, needing extensive tests in petri dishes, cells, animals, young male human volunteers, and then mass drug trials. It is very slow and challenging work to find new drug molecules that are both safe and effective.…

Where is a good area to begin studying computer modeling/testing for pharma?

Re: Anti-diarrhoea drug drives cancer cells to cell death

#53

Post by endymi0n »

wittyreference wrote: post #6

Several classes of opioids have been shown to cause neuronal degeneration via ATF4 activation. So, key points: 1. Loperamide is not unique. I don't know why these researchers have singled it out. Is it because they heard there's an opioid that doesn't get you high? It only avoids getting you high because it doesn't get into the brain. IF you deliver it to the brain to treat a brain tumor, it will get you high. 2. Pat…

And this is just a view limited to opioids. In general, there is no shortage of compounds with an ability to kill cancer cells since the 1950s.

The grand (and still largely unsolved) challenge is not killing them, it‘s sparing the rest of the body while doing so.

Re: Anti-diarrhoea drug drives cancer cells to cell death

#54

Post by weare138 »

wittyreference wrote: post #6

Several classes of opioids have been shown to cause neuronal degeneration via ATF4 activation. So, key points: 1. Loperamide is not unique. I don't know why these researchers have singled it out. Is it because they heard there's an opioid that doesn't get you high? It only avoids getting you high because it doesn't get into the brain. IF you deliver it to the brain to treat a brain tumor, it will get you high. 2. Pat…

Ok, so I'm not a doctor or anyone with actual expertise in this area (I'm just a weirdo that reads way to much) and I am no way trying to challenge your expert opinion but I do have a question. Could the the result be attributed to something unique to loperamide's molecular structure versus traditional opioids? Again not an expert on this topic, but looking at the molecular structure of loperamide compared to organic derived opioids (opium, heroin, codeine, etc) or synthetic opioids like oxytocin, loperamide's molecular structure is markedly different. Could there be some other factor at play here?

Re: Anti-diarrhoea drug drives cancer cells to cell death

#55

Post by bilekas »

ar-jan wrote: post #28
wittyreference wrote: post #6

Several classes of opioids have been shown to cause neuronal degeneration via ATF4 activation. So, key points: 1. Loperamide is not unique. I don't know why these researchers have singled it out. Is it because they heard there's an opioid that doesn't get you high? It only avoids getting you high because it doesn't get into the brain. IF you deliver it to the brain to treat a brain tumor, it will get you high. 2. Pat…

> It only avoids getting you high because it doesn't get into the brain. People do get high on immodium [0]. With huge doses, but still. 0: https://www.forbes.com/sites/robertglatter/2018/01/31/fda-cr...

> People do get high on immodium

This is wild. I had no idea! How does one even discover that?

Re: Anti-diarrhoea drug drives cancer cells to cell death

#56

Post by gregwebs »

Dumblydorr wrote: post #20

There is incredible potential out there, potentially dozens of useful treatments that are safe and cheap, and all we have to do is repurpose them. Consider that new drugs cost 1 to 2 billion to come to market, needing extensive tests in petri dishes, cells, animals, young male human volunteers, and then mass drug trials. It is very slow and challenging work to find new drug molecules that are both safe and effective.…

How would you turn this into a gold mine? As I understand it the opportunity for off-label drug use is limited. Although the off-label drug will be cheaper to bring to market the patent will expire and then you can no longer recoup the enormous cost of clinical trials.

Re: Anti-diarrhoea drug drives cancer cells to cell death

#57

Post by curious_fella1 »

wittyreference wrote: post #45
curious_fella1 wrote: post #32

Earlier quoted context omitted.

> Several classes of opioids have been shown to cause neuronal degeneration Question for you - is this "brain damage" that I often hear results from taking a particular drug the result of intentful downregulation of certain neuronal receptors (e.g., meth -> too much dopamine in synapse -> downregulate dopamine receptors), or is the drug actually killing brain cells/neurotoxic?

That's an excellent question, and an area of active research. It differs a lot by drug, though, because of their affect on different signaling systems, different neurons, and due to indirect damage to the brain from effects elsewhere in the body: 1. E.g., cocaine as a strong vasoconstrictor can directly cause cerebral ischemia, causing hypoxic damage to the brain. Acute hypoxic damage is relatively uncommon, but atro…

Thank you for the comprehensive response! That was very interesting :)

I took a Biopsychology of Drugs class in college and found it fascinating. Do you know of any good (text)books on the subject?

Re: Anti-diarrhoea drug drives cancer cells to cell death

#58

Post by Supermancho »

wittyreference wrote: post #48
Supermancho wrote: post #44

Earlier quoted context omitted.

> Loperamide is not unique. I don't know why these researchers have singled it out. Probably because it's what they were studying which led to the analysis? A drug doesn't have to be unique to be important in understanding side effects...or off-label use if that's how you want to think of it. Getting funding to study all of them at once is more challenging, so it shouldn't be a surprise that it's constrained to one.

Opioids have already been studied regarding their neurotoxic effect. We already know they are neurotoxic. We already know they use the ATF4 pathway. Loperamide is an opioid. It's like a study finding that "opioid X" gets you high via mu-opioid receptors. It's not really a finding; it's the null hypothesis.

> It's like a study finding that "opioid X" gets you high via mu-opioid receptors. It's not really a finding; it's the null hypothesis.

More likely it's a liability check. The null hypothesis characterization is incidental.

Re: Anti-diarrhoea drug drives cancer cells to cell death

#60

Post by wittyreference »

weare138 wrote: post #54
wittyreference wrote: post #6

Several classes of opioids have been shown to cause neuronal degeneration via ATF4 activation. So, key points: 1. Loperamide is not unique. I don't know why these researchers have singled it out. Is it because they heard there's an opioid that doesn't get you high? It only avoids getting you high because it doesn't get into the brain. IF you deliver it to the brain to treat a brain tumor, it will get you high. 2. Pat…

Ok, so I'm not a doctor or anyone with actual expertise in this area (I'm just a weirdo that reads way to much) and I am no way trying to challenge your expert opinion but I do have a question. Could the the result be attributed to something unique to loperamide's molecular structure versus traditional opioids? Again not an expert on this topic, but looking at the molecular structure of loperamide compared to organic…

Challenge away, it's the internet!

I think that it's possible but unlikely that loperamide is having a unique effect, because (a) they've shown that it's operating via the ATF4 mechanism, which is the same mechanism we see in other opioids (and multiple other drugs), and (b) loperamide's activity has generally been pretty well characterized and it doesn't really stand out (it's by no means a new drug - I remember taking it as a generic twenty years ago.)

I'll admit it's possible in the broad sense because ATF4 isn't some super-specific pathway. It's a stress response signal. So while I think (b) above makes a unique mechanism unlikely, (a) by itself isn't a slam-dunk - there are a lot of stress signals that induce cell death when they get amped up enough, and can inhibit cell death if blocked off.

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