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Oral cancer drug kills 100% of tumors in vitro and in animal models

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Re: Oral cancer drug kills 100% of tumors in vitro and in animal models

#51

Post by deep_merge »

Terr_ wrote: post #27
isoprophlex wrote: post #12

https://en.m.wikipedia.org/wiki/AOH1996 Look at that molecular structure. Incredible. Two amide bonds, a completely unremarkable aryl ether and an unsubstituted naphthalene ring system. No fussy weird metals or bonds that need pampering, no chiral carbon atom in sight. You could probably pay someone a very modest amount of money to end up with kilograms of this stuff, and it would probably not degrade at all under am…

> Look at that molecular structure. Incredible. Two amide bonds, a completely unremarkable aryl ether and an unsubstituted naphthalene ring system. Something about this delivery reminds of the business-card scene from Psycho [0]. > Look at that subtle off-white coloring, the tasteful thickness of it--Oh my God, it even has a watermark..." [0] https://www.youtube.com/watch?v=cISYzA36-ZY

*American Psycho. Dude in Psycho didn’t use a business card.

Re: Oral cancer drug kills 100% of tumors in vitro and in animal models

#52

Post by sp332 »

danielvaughn wrote: post #47
zer8k wrote: post #36

Given the importance of this medication and it's promising initial data I have no idea why it's not given "warp speed" clearance. We cleared mRNA technology almost overnight in response to the pandemic. I feel like society as a whole has collective amnesia on how this happened. A relatively novel strategy to rapidly produce a vaccine in response to a pandemic was trialed essentially on a global scale. The phase 1/2/3…

Agreed; it should at least match the energy devoted to superconductivity.

Well if that's what you're looking for, Martin Shkrelli is spitefully publishing a bunch of related molecules to deny prior art claims. https://twitter.com/wagieeacc/status/1687137621699436552

Re: Oral cancer drug kills 100% of tumors in vitro and in animal models

#53

Post by BenFranklin100 »

kybernetikos wrote: post #49
isoprophlex wrote: post #12

https://en.m.wikipedia.org/wiki/AOH1996 Look at that molecular structure. Incredible. Two amide bonds, a completely unremarkable aryl ether and an unsubstituted naphthalene ring system. No fussy weird metals or bonds that need pampering, no chiral carbon atom in sight. You could probably pay someone a very modest amount of money to end up with kilograms of this stuff, and it would probably not degrade at all under am…

Derek Lowe had a similar take: "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." https://www.science.org/content/blog-post/new-mode-cancer-tr...

A key sentence:

“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.”

Even if this does prove effective in humans, eventually cancer cell defenses will evolve to get around it.

Re: Oral cancer drug kills 100% of tumors in vitro and in animal models

#54

Post by ugh123 »

jjtheblunt wrote: post #15

Absolute clickbait fraudulent title. From the article in Cell: "Given orally, AOH1996 suppresses tumor growth but causes no discernable side effect" is a VERY different result.

Clickbait? Maybe. But fraudulent? Hyperbole much?

Re: Oral cancer drug kills 100% of tumors in vitro and in animal models

#57

Post by szundi »

BenFranklin100 wrote: post #53
kybernetikos wrote: post #49

Earlier quoted context omitted.

Derek Lowe had a similar take: "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." https://www.science.org/content/blog-post/new-mode-cancer-tr...

A key sentence: “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.” Even if this does prove effective in humans, eventually cancer cell defenses will evolve to get around it.

Goal is to die for some other reason before cancer evades this

Re: Oral cancer drug kills 100% of tumors in vitro and in animal models

#58

Post by solomatov »

BenFranklin100 wrote: post #53
kybernetikos wrote: post #49

Earlier quoted context omitted.

Derek Lowe had a similar take: "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." https://www.science.org/content/blog-post/new-mode-cancer-tr...

A key sentence: “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.” Even if this does prove effective in humans, eventually cancer cell defenses will evolve to get around it.

>Even if this does prove effective in humans, eventually cancer cell defenses will evolve to get around it.

Cancer becomes tolerant to drugs separately for each patient. I.e. initially it isn't resistant, but the drug used on a patient puts evolutionary pressure on the cancer to work around the drug. What this means is that people have more months or years to live, which is great. (I am not a doctor).

Re: Oral cancer drug kills 100% of tumors in vitro and in animal models

#59

Post by ncann »

isoprophlex wrote: post #12

https://en.m.wikipedia.org/wiki/AOH1996 Look at that molecular structure. Incredible. Two amide bonds, a completely unremarkable aryl ether and an unsubstituted naphthalene ring system. No fussy weird metals or bonds that need pampering, no chiral carbon atom in sight. You could probably pay someone a very modest amount of money to end up with kilograms of this stuff, and it would probably not degrade at all under am…

> I wouldn't be surprised if we soon see desperate, sick, rich people try this out on themselves, skipping FDA approval

I know nothing about the FDA but for things like terminal cancer treatment, shouldn't there be a blanket exemption for "if the patient so wish, they can take whatever drugs they want even if unapproved"? When facing certain death, what's the worst that can happen? You die a bit sooner?

Re: Oral cancer drug kills 100% of tumors in vitro and in animal models

#60

Post by mbreese »

isoprophlex wrote: post #39
teruakohatu wrote: post #37

Earlier quoted context omitted.

Can you explain to a layman why works to kill tumors and not healthy cells?

The idea is that cancer cells have this mutant DNA clamp[0], which rallies DNA repair mechanisms in cells. The molecule targets the mutant clamp, disabling repair mechanisms for tumor cells but not healthy cells. We all should hope that it has high specificity for the mutant PCNA, and doesn't affect healthy cells... clinical trials will investigate this. [0] https://en.m.wikipedia.org/wiki/Proliferating_cell_nuclear_…

I don’t think this is targeting a mutated version of PCNA… that would assume that all cancers had the same mutation.

Instead, this would target both healthy and cancerous cells. However, the idea is that the cancer cells are more susceptible to the drug. Healthy cells will be affected, but cancer cells will be affected more, and are more unstable, so losing PCNA will have more of an effect on the cancer cells.

The main idea is to do as much damage to the cancer cells while doing as little to normal cells as possible.

Edit: after reading the paper, the drug is targeting a cancer specific isoform of PCNA. This isn’t a mutation, but a slightly different form of the existing protein. Cancers tend to rely on this specific version, while healthy cells can use a different isoform (or both?). A selective inhibitor for this isoform would be cancer cell specific. There would still be some effect on healthy cells, but not as much as with a traditional cytotoxic chemotherapy.

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