A New Mode of Cancer Treatment 36
As detailed in a paper published in Cell Chemical Biology, researchers have developed a "cancer-killing pill" capable of destroying solid tumors while leaving healthy cells unaffected. The new drug has been in development for 20 years and is now undergoing pre-clinical research in the U.S.. Derek Lowe, a medicinal chemist and freelance writer on science and pharmaceutical topics, writes about the new paper via Science Magazine: It's about a molecule designated AOH1996, which seems to have a unique mode of action in tumor cells, one that might make it more more selective for those as compared to normal ones. The key target here is a protein called PCNA (from its old name of "proliferating cell nuclear antigen"). [...] The current molecule is a traditional direct small molecule binder that is selective for caPCNA over the regular type, which is a very attractive advantage to explore. The team behind it has been working on it for several years now to validate that mechanism, and the new paper linked first above is their report of going all the way into animal models. AOH1996 is a very unremarkable-looking molecule - to be honest, it looks like the sort of stuff that you used to see in old combinatorial chemistry libraries in the late 90s and early 2000s, a couple of aryl-rich groups strung together with amide bonds. It's certainly not going to be the most soluble stuff in the world, but they seem to have been able to formulate it. But I'm definitely not going to make fun of any chemical structure that works! [...]
The new paper shows preclinical toxicity testing in two species (mice and dogs), which is what you need to get to human trials. It seems to pass those very well, with no signs of trouble at 6x the effective dose in either species. And if you were throwing DSBs all over the place in normal tissues, believe me, you'd see tox. It is clean in an Ames test, for example. As for efficacy, in cell assays the concentration needed for 50% growth inhibition across 70 different cancer cell lines averaged around 300nM, while it showed no toxic effects on various non-cancer lines up to 10 micromolar (at least a 30x window). The affected cells show cell-cycle arrest, replication stress, apoptosis, and so on. And application of AOH1996 along with other known chemotherapy agents made the cells much more sensitive to those, presumably because they couldn't deal with those on top of the problems that AOH1996 was already causing.
It also shows growth arrest in xenograft tumors in mouse models, with a no-effect dose at least six times its effective dose, and combination therapy with a topoisomerase inhibitor showed even more significant effects. The compound has entered a Phase I trial in humans on the basis of the above data, and I very much look forward to seeing it advance to Phase II, where it will doubtless be used in combination with several existing therapies. I hope that human cancers will prove vulnerable to this new mode of attack in the clinic, and that they are not able to mutate around it with new forms of caPCNA too quickly, either. The comparison with the peptide agent mentioned above will be especially interesting, too. There's only one way to find out - good luck to everyone involved!
The new paper shows preclinical toxicity testing in two species (mice and dogs), which is what you need to get to human trials. It seems to pass those very well, with no signs of trouble at 6x the effective dose in either species. And if you were throwing DSBs all over the place in normal tissues, believe me, you'd see tox. It is clean in an Ames test, for example. As for efficacy, in cell assays the concentration needed for 50% growth inhibition across 70 different cancer cell lines averaged around 300nM, while it showed no toxic effects on various non-cancer lines up to 10 micromolar (at least a 30x window). The affected cells show cell-cycle arrest, replication stress, apoptosis, and so on. And application of AOH1996 along with other known chemotherapy agents made the cells much more sensitive to those, presumably because they couldn't deal with those on top of the problems that AOH1996 was already causing.
It also shows growth arrest in xenograft tumors in mouse models, with a no-effect dose at least six times its effective dose, and combination therapy with a topoisomerase inhibitor showed even more significant effects. The compound has entered a Phase I trial in humans on the basis of the above data, and I very much look forward to seeing it advance to Phase II, where it will doubtless be used in combination with several existing therapies. I hope that human cancers will prove vulnerable to this new mode of attack in the clinic, and that they are not able to mutate around it with new forms of caPCNA too quickly, either. The comparison with the peptide agent mentioned above will be especially interesting, too. There's only one way to find out - good luck to everyone involved!
Maybe they should put it in the new Chevron fuel (Score:1)
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So, punk, feelin' lucky?"
Good timing (Score:3)
Maybe it will prove helpful in combating all the cases of cancer we can expect to see because of the EPA's recent fuckup [slashdot.org].
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Really? Because the molecular structure is published and so are these studies. In other words, anyone motivated can make it for themselves. You're telling me China and India etc. are going to pay? Get real.
Wow (Score:3)
Long time no see, the anti-cancer pill.
How many animals did they give cancer to? (Score:1)
Why do I recoil at any treatment with so much murder behind it? Can you just legalize drugs so I can self-medicate, please?
Re: How many animals did they give cancer to? (Score:1)
Re: How many animals did they give cancer to? (Score:2)
Does it bother you that cannabis is legal now in this state?
Re: How many animals did they give cancer to? (Score:2)
Why am I imagining a sadistic sociopath gleefully chortling at the thought of giving innocent animals cancer, for "thienthe"?
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Re: How many animals did they give cancer to? (Score:2)
Why not human babies, then?
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Do you eat meat, or do you starve the animals to death by eating plants?
Re: How many animals did they give cancer to? (Score:2)
How come my recent campsite was surrounded by huckleberry, salmonberry, eldeberry, etc. so that no one was starved?
Re: How many animals did they give cancer to? (Score:1)
Wouldn't the universe just be a whole lot better off if hu-mans go extinct?
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Probably not. Animals are not exactly kind to each other. Watch more nature videos.
Patent (Score:2)
Here's the patent on it. https://patents.google.com/pat... [google.com]
call me when it finishes clinical trials (Score:5, Insightful)
It's not even in clinical trials yet, only "pre-clinical" which I gather means no humans. The vast majority of new drugs never make it through clinical trials. This is basically a press release to gin up a stock price, best I can tell.
Re: call me when it finishes clinical trials (Score:2)
How many animals must die for shareholder equity to grow?
Re:call me when it finishes clinical trials (Score:4, Informative)
From the article:
The compound has entered a Phase I trial in humans on the basis of the above data
And no, it's not a press release. Derek Lowe is a very well known writer who has been reporting on issues related to the pharmaceutical industry for many years. Almost everyone in the field reads his blog.
Now we wait for the patents to expire (Score:2)
So the rest of us can afford to be treated with it.
Why can't terminally ill people test this? (Score:2)
But AFAIK tests like that are not done.
Why not?
Re: Why can't terminally ill people test this? (Score:3)
The Phase I trial is scheduled to finish next year. After that point, it may become available under compassionate use or right-to-try laws. However, there are strict procedures to reach these, and production volumes during trials are very low, so most won't have access even if they qualify.
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It's targeting a protein that is present and active in every cell of the body (except maybe red blood cells, which ditch their nucleus soon after forming). If it doesn't go well, it could kill the patient quickly through cascading organ failure.
On the other hand, if this works, the drug company can very nearly print money. It may cure cancer, but it won't stop cancer from forming, and it can just keep going for as long as patent protection holds out (which drug companies are extraordinarily good at extendin
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So get it into terminally ill patients, yesterday.