Talk:AOH1996

News articles about this drug are factually incorrect if you read the original article in Cell

I am extremely alarmed by the media overhype surrounding this drug. News articles suggest "annihilates" 70 different kinds of cancer, which is simply not correct if you read the original paper (https://www.cell.com/cell-chemical-biology/pdfExtended/S2451-9456(23)00221-0).

AOH1996 was evaluated against a 60 cell panel and shown to have a GI50 concentration of around 300nM for all of them, which is significantly lower than that of some existing FDA approved cancer drugs for the same panel. For example, bortezomib has a GI50 across the board against the same set of cell lines in the 1-10nM range (see figure 4 of https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868078/).

AOH1996 has only been tested against THREE kinds of xenograft solid tumors, and was only very effective against TWO of those three (see figure 4C-D of the original paper). The only in vivo data was done for neuroblastoma tumors, and there was no significant difference in survival unless it was combined with an established cancer therapeutic (figure 4H of original peper). It was only tested with 8 mice in each condition anyway! Palmerito0 (talk) 16:58, 4 August 2023 (UTC)

I think you are making a mountain out of a mole hill. There has not be widespread media coverage of this report, with the exception that the inventor was interviewed by Fox News Radio (I heard it). Scanning Twitter, the coverage is largely by irrelevant alternative media, and not very extensive at that. This is no Judah Folkman-Endostatin-Nature fiasco with the NY Times and Wall Street freaking out about something that never worked in the clinic (although it worked much much better in mice than AOH1996).

As far as the science goes. It is being developed by the National Cancer Institute. There's a reason for that. Anyone who is a serious drug developer is not that excited by it, and likely no Pharma was when they were approached by City of Hope to outlicense it. If the inventor tried to start a company around it, apparently no venture capitalists were interested in investing. NCI is what's left.

It is an interesting paper. There may be some utility eventually, but the odds are against it, like most cancer drugs in clinical trials (95% failure rate). Someone may be able to take these ideas and do something with it, who knows.

The NCI60 panel that was run has been run for >100,000 compounds over the last several decades. Activity in that panel has never predicted anything in the clinic. Mentioning that it is "active in more than 70 types of cancer" is therefore a red herring. More interesting is the lack of activity in normal cells.

As you not, the in vivo data in mouse models of cancer is pretty mediocre. Not a single model demonstrated stable disease, partial responses or complete responses, which is what you need for success in the clinic. Granted, these models (unlike patient-derived xenograft models) do not predict clinical results. But lack of substantial activity in these models is a bad sign.

Personally, I wouldn't develop this drug. I would explore better ways to use it (perhaps drug combinations) or the the concept of a tumor selective form of PCNA. But I can think of many more promising drugs that are currently in clinical testing, none of which are described as a "Cure for All Cancer".

If it really was a "cure for all cancer", it wouldn't be published in this journal, which is a specialist chemical biology journal, although respected. They may well have submitted it to a more prestigious journal and been turned down, or didn't submit it because they recognized that it would likely be turned down for lack of broad significance.

Paper:

https://www.cell.com/cell-chemical-biology/pdfExtended/S2451-9456(23)00221-0

Nothing to be alarmed about, or unfortunately excited about. BostonBestEats (talk) 06:12, 5 August 2023 (UTC)

I am a bit surprised by Derek Lowe's fairly positive take on it (referenced in Wiki page), since he usually has good taste in pharmaceutical science. But he's a chemist and may be excited by a novel chemical approach.

BTW, 8 mice per group in the mouse studies is typical and accepted for FDA IND-enabling studies, so nothing to be concerned about there. The number of models run 3 (1 in both tumor growth inhibition and survival modes) is typical too. BostonBestEats (talk) 06:22, 5 August 2023 (UTC)

Hmm, I see 530k+ results on Google for "AOH1996", some of them from larger news outlets (New York Post, Jerusalem Post, The Independent), and it's only been a few days. There definitely is a good bit of reporting being put out about it, and it almost all repeats the same claim about it "annihilating" 70 different kinds of cancer. I guess I'm just frustrated to see this as I expect (though I admit this isn't realistic) better from journalists covering science. I was especially frustrated to see a biologist I follow on Twitter regurgitating this misinformation to an audience of 200k+. Brought it to their attention and they said they'd issue some sort of correction/amendment, but they still haven't and I doubt they ever will.

And yeah, I'm aware that 8 mice per group is typical, I only highlight it to emphasize that the evidence for this drug's efficacy is limited.

I honestly don't know much about the business side of pharmaceuticals, thank you for the insights re: licensing. My hope is that this turns out to have a low enough toxicity to serve as a "booster" for use with other chemotherapies that induce DSBs/DNA damage in general, so I'm glad NCI is still giving it a follow-up. Palmerito0 (talk) 22:33, 5 August 2023 (UTC)

@Palmerito0 i also didnt like the news,for trying to get only attantion out of things that arent realistic and fake. Struppig taucher (talk) 23:58, 12 August 2023 (UTC)

dont like them for faking multiple thing s,like the "info" about the drug.* Struppig taucher (talk) 00:00, 13 August 2023 (UTC)

Well, I don't think there is anything actually fake about what they've said or published. Just imagine you are a grad student or postdoc, or a professor or research institute. You are all desperate for funding for your reseach, in an environment where the NIH turns down 80% of the grant applications it receives. You discover something cool, so you send out a press release. It's your 15 minutes of fame, and maybe it will attract some funding (like the $25,000 from the parents of a dead child who walked into this professor's lab right off the street). They can't help it if the media hypes things out of proportion to get clicks or plays up things like the 70 cell lines that everyone will misinterpret. This happens all the time. The media needs their feel good stories. But don't pay attention until the drug gets approved. BostonBestEats (talk) 17:03, 13 August 2023 (UTC)