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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

#101

Post by piyh »

mbreese wrote: post #60
isoprophlex wrote: post #39

Earlier quoted context omitted.

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 ma…

>"Moreover, the identification of a distinct isoform of PCNA associated with cancer cells has potentially opened a novel avenue for the development of new chemotherapeutics"

It is targeting a mutated version.

https://www.cell.com/cell-chemical-biology/fulltext/S2451-94...

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

#102

Post by mbreese »

piyh wrote: post #101
mbreese wrote: post #60

Earlier quoted context omitted.

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 ma…

>"Moreover, the identification of a distinct isoform of PCNA associated with cancer cells has potentially opened a novel avenue for the development of new chemotherapeutics" It is targeting a mutated version. https://www.cell.com/cell-chemical-biology/fulltext/S2451-94...

A distinct isoform does not necessarily mean a mutation.

The coding sequence for an isoform is part of the normal gene DNA sequence, but the cells can “choose” which version to make. In this case the caPCNA isoform is the form predominantly expressed in cancer cells.

(There is a mechanism where novel splicing isoforms can be produced by a mutation, but this doesn’t seem to be one of those.)

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

#103

Post by jjtheblunt »

ugh123 wrote: post #54
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?

Hyperbole expands a truth; that title states a falsehood (see the paper) as true.

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

#104

Post by Terr_ »

nine_k wrote: post #83
Terr_ wrote: post #27

Earlier quoted context omitted.

> 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

Only it's the inverse: no subtlety, no surprises, all plain.

I'm not sure I'd describe that scene as actually containing amazing surprises of printing, typography, or subjective stylishness.

I see it as mockery of some maladjusted status-obsessed men as they fawn and suffer over trivial differences in pretty-much-identical plain white business cards. Every card says the same thing except for the name, and many of the things being described aren't even true. (For example, not embossed, no watermark, etc.)

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

#105

Post by rdsubhas »

jjtheblunt wrote: post #99
thebradbain wrote: post #84

Earlier quoted context omitted.

Suppressing tumor growth is how you kill cancer, is it not? Cancer cells themselves, like the original cells they mutate from, don't live forever. Depending on which type of cell we're talking about, they can die within hours (e.g. skin cells)/days (e.g. blood cells)/months (e.g. liver cells). The issue with cancer cells is they are reproducing like crazy way faster than they die, which is why the tumors grow bigger…

suppressing growth does not equate to 100% regression. the growth rate could be suppressed to match the attrition rate and turn into a steady state, rather than eradication of the mutant cell lines (and their progeny).

If it turns into a controlled steady state, does it still fit the medical definition of cancer?

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

#106

Post by mrklol »

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…

Okay, forgive me for this stupid question but my biology level isn’t that great.

But, if we know which cells to target and what their structure is, can’t we just extract some healthy cells, reproduce them, kill all cells which would dock to that pill, insert reproduced healthy cells?

So with that we don’t have to care if it attacks healthy cells, or is that reproduction idea not possible?

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

#107

Post by jjtheblunt »

rdsubhas wrote: post #105
jjtheblunt wrote: post #99

Earlier quoted context omitted.

suppressing growth does not equate to 100% regression. the growth rate could be suppressed to match the attrition rate and turn into a steady state, rather than eradication of the mutant cell lines (and their progeny).

If it turns into a controlled steady state, does it still fit the medical definition of cancer?

good question, but cancer is generally replicating aneuploidy, so it's curious for sure

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

#108

Post by fnordpiglet »

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…

Two speculative substances, this and LK99, are both simple and cheap the synthesize. If either pan out it’s a miracle for man kind. But, it leaves me to wonder, what shenanigans will corporations go through to make it inaccessible and expensive?
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