6 ms·
Drug trio found to block tumour resistance in pancreatic cancer in mouse models
- jonshariat 8mo agoI've been playing to much pokemon with my kids, read this as "Dugtrio"
- j-bos 8mo agoSame, I'll never look at them the same again.
- JohnMakin 8mo agome too
- m463 8mo agothere must be some sort of word for "games-bleeding-into-real-life" for stuff like this. I remember years ago playing some games, and hearing similar sounds in real life would startle (or amuse) me. And you can't really explain it to anyone around you, lol.
- braedonwatkins 8mo agotetris effect! https://en.wikipedia.org/wiki/Tetris_effect https://en.wikipedia.org/wiki/Tetris_effect
- m463 8mo agoWow that article is very thought provoking! and hilarious, like the toilet paper orientation article: https://en.wikipedia.org/wiki/Toilet_paper_orientation https://en.wikipedia.org/wiki/Toilet_paper_orientation
- bitwize 8mo agoThere's an elevator in a building where I attend meetups. A staffer has to authenticate with a card in order to let you use the elevator. Once it authenticates, a chime plays that goes sol-do-mi-sol. These four notes also begin the main bit of the Super Mario Bros. 2 overworld theme which I find myself humming.
- tyre 8mo agothank you, I did a double take. Drugtrio is my new favorite Pokémon
- dystopiandevel 8mo agoIt's okay, I thought it was a drug cartel
- ngriffiths 8mo agoIN MICE. (To be fair, also IN SOME OTHER BETTER MICE). https://jamesheathers.medium.com/in-mice-explained-77b61b598218 https://jamesheathers.medium.com/in-mice-explained-77b61b598... (mostly a joke, but I'd be in favor of adding context to the HN headline if possible)
- apparent 8mo agoThis isn't quite as bad as the garden variety "in mice" studies: > The combination therapy also led to significant regression in genetically engineered mouse tumours and in human cancer tissues grown in lab mice, known as patient-derived tumour xenografts (PDX).
- ramesh31 8mo ago>"The combination therapy also led to significant regression in genetically engineered mouse tumours and in human cancer tissues grown in lab mice" Required XKCD: https://xkcd.com/1217/ https://xkcd.com/1217/
- stultissimus 8mo agoPDX is a double edged sword. Human tumors are engrafted into mice with no immune system. Immune-cancer interface is incredibly important, yet completely lacking in these models. Consider that some of the greatest cancer drugs ever work specifically on the immune system (e.g. checkpoint inhibitors like Keytruda).
- reenorap 8mo agoI keep reading about these advancements in pancreatic cancer like early detection or possible treatments, but nothing ever seems to make it to daylight. Is there a reason why there's such disparity between this?
- ngriffiths 8mo agoBecause research on real humans and real diseases is exceptionally difficult. Clinical research is notoriously expensive, results are likely to differ from non-human (preclinical) models, and trials take forever to get started, gather enough data, and get a drug actually reviewed and approved. So even when everyone is excited by the preclinical data, there are so many barriers (both scientific and non-scientific) that getting to an approved drug is pretty unlikely.
- dyauspitr 8mo agoWe really should be able to grow human bodies without a brain for testing purposes. It’s gruesome but realistically victimless at the end of the day.
- ngriffiths 8mo agoI don't think the biology is there, let alone consensus on the major ethical questions involved
- giardini 8mo agoCan you imagine the political/religious push-back were you to do that?! Growth of single human organs or organ tissue is easier, cheaper and less fraught with political peril.
- baka367 8mo agoAs someone whose mother died to pancan, I could really care less on any of the brainwashed old farts in their churches or parliaments. None of that matters to me or the people suffering from cancers, it’s al Knut a selfish obstruction attaching religion to the research material
- gus_massa 8mo ago> The results demonstrated the therapy not only reduced tumour size but also entirely stopped tumour growth with no evidence of tumour resistance for more than 200 days after treatment. More details in https://www.pnas.org/doi/suppl/10.1073/pnas.2523039122/suppl_file/pnas.2523039122.sapp.pdf https://www.pnas.org/doi/suppl/10.1073/pnas.2523039122/suppl... See page 25 In mice, N=12. 1 survived 200 days without cancer and was euthanized for 'ocular ulcers'. 5 survived 50-150 days, without cancer but were euthanized for other health problems 6 survived 50-150 days, and still had a smaller tumor and were euthanized for other health problems My take away: Interesting, but the press article is overselling the result by a lot. Edit: Fixed link.
- apparent 8mo agoApparently 50 mice days is equivalent to about 5 human years, so even if these other causes of death here directly caused by the treatment (not alleged), surviving this much longer (5-20 years) would be pretty incredible for humans.
- gus_massa 8mo agoWhere did you get that "50 mice days is equivalent to about 5 human years"? Mice are short lived, so the time for some events like sexual maturation are shorter. On the other hand, the problem with cancer is that it adapts, it "learn" how to avoid the effect of the drugs, or how to make the signals to get more blood vessels, or ... I think most of these only depend on how many times the cancer cells reproduce to get a lucky adaptation, so for these effects 200 days is only 200 days. Also survival rate depends on how early it's detected. In a recent post about colon cancer, the mice got the treatment like 2 weeks after the cancer cells were injected. My guess is that this study also has a short time before the treatment. Early detection improves survival rate a lot: https://www.cancerresearchuk.org/about-cancer/pancreatic-cancer/survival https://www.cancerresearchuk.org/about-cancer/pancreatic-can... > Localised: More than 25 out of 100 people (more than 25%) survive their cancer for 3 years or more after diagnosis. > Regional: Around 15 out of 100 people (around 15%) survive their cancer for 3 years or more after diagnosis. > Distant: Only 1 out of 100 people (1%) survive their cancer for 3 years or more after diagnosis.* Also (combining all detection stages): > Generally for adults with pancreatic cancer in the UK: > around 5 out of every 100 (around 5%) survive their cancer for 10 years or more
- lazarus01 8mo agoI was wondering what preclinical models meant. It would be more accurate to call it animal models. I read roughly 3% - 5% of compounds move from preclinical cancer therapies to fda approval. That’s a tough success rate.
- boh 8mo agoIt's funny how many years of "X found to be effective in fighting cancer" stories have filtered through HN and then you never hear about it again. The research at treating mouse cancer has been making great strides--people cancer still has a long way to go though.
- adrianN 8mo agoPeople cancer outcomes have improved a lot in recent decades. Many forms of cancer are essentially cured if you detect them early enough.
- unsupp0rted 8mo agoWhat's the best protocol for detecting them early enough, as an annual set of tests that a non-crazy / non-rich person would go do?
- delecti 8mo agoI have absolutely no idea what the current frontline treatment drugs are for literally any form of cancer, and would bet the same is true for almost everyone else here. Most of the exceptions are people who know the frontline treatment drugs for one or two forms of cancer that impacted them personally. "And then you never hear about it again" is subtly implying that the drugs behind headlines never proceed beyond that point, but I didn't hear about it when the current frontline became the frontline treatment for any form of cancer. Most people just aren't in the loop about the evolution of the field of oncology, beyond pop-sci headlines. And yes, most headlines like this don't result in changes to the care provided to anybody outside of clinical trials, but some do, and you and I probably won't hear about those either.
- dekhn 8mo agoI think this is one of the expected outcomes of "Science by Press Release" (universities motivated to maximize their grants and IP), combined with media/press that wants clicks (articles that talk about cures for cancer get clicks).
- inglor_cz 8mo ago
- apparent 8mo ago> These agents together were tested in orthotopic mouse models of PDAC, where tumour cells are implanted in a location that closely resembles their natural environment in the pancreas. Ugh, of course: "in mice"! > The combination therapy also led to significant regression in genetically engineered mouse tumours and in human cancer tissues grown in lab mice, known as patient-derived tumour xenografts (PDX). OK, maybe "in human tissue grown in mice" isn't so bad. Fingers crossed. Pancreatic cancer is terrible.
- tansey 8mo agoFor all the folks complaining about "it's only in mice! things never work in humans!" -- I work at MSK and we definitely have seen success treating PDAC in humans: https://www.nature.com/articles/s41586-023-06063-y https://www.nature.com/articles/s41586-023-06063-y "Why don't I see these treatments hitting the general public?" Because trials like these are phase I/II. Then you need a phase III that takes a long time to recruit a large cohort and has overall survival as an end point so you need a long time to measure the actual outcome you care about. And most trials fail in phase III because the surrogate end points used in phase II studies, like progression free survival (ie how long did patients go before their disease advanced in screens), are not necessarily great predictors of improved overall survival. Specifically for cancer vaccines, this paper was a driving force behind MSK establishing a cancer vaccine center to scale up these personalized neoantigen mRNA vaccines. It's very very difficult to do and extremely expensive right now.
- jjtheblunt 8mo agoWhat's MSK?
- packetslave 8mo agoright-click, search Google: "MSK most commonly refers to Memorial Sloan Kettering Cancer Center, a world-renowned institution for cancer treatment and research"
- whizzter 8mo agoThe first co-author of the linked paper is also associated with MSKCC.
- jjtheblunt 8mo agocool...so random i hadn't thought to right click, but thanks because while right under my nose and overlooked, it's useful to know now!
- _zagj 8mo agoMemorial Sloan Kettering, one of the NCI(National Cancer Institute)-Designated Cancer Centers. If you're getting treated for cancer, the NCI-Designated Cancer Centers are usually your best bet.
- tiahura 8mo agoAt this point, hasn't every permutation of cancer drug cocktail been tested on mice?
- A_D_E_P_T 8mo ago> Clinical implications: While more research will be needed before trials in humans can begin Why? Seriously, think about it. Most people with pancreatic cancer have nothing to lose and many of them have just weeks or months to live. Daraxonrasib, Afatinib, and SD36 are molecules that can already be purchased in bulk, and what's the worst that can happen? Our society's morbid, irrational fear of quack medicine causes orders of magnitude more deaths through therapeutic neglect than it prevents through safety screening. "Better 10,000 die of cancer than 1 person die of fraud/waste/mismanagement or even in failed experiments performed in good faith."
- snapcaster 8mo agoYeah putting myself in the shoes of someone with this disease or a loved one with this disease I would be so incredibly angry that we weren't allowed to try something when the alternative is certain death
- reg_dunlop 8mo agoIt's the prisoner's dilemma. Or more succinctly: Take something and possibly live, or take nothing and certainly die.
- bobbylarrybobby 8mo agoThat's not what the prisoner’s dilemma is.
- petcat 8mo agoYeah this is more like a Pascalian Gamble [1]. If you try nothing, then you are assured to die as God wanted. If you try something, then you might live, but then God hates you. [1] https://en.wikipedia.org/wiki/Pascal%27s_wager https://en.wikipedia.org/wiki/Pascal%27s_wager
- deleted 8mo ago[deleted]
- Tade0 8mo agoRecently YouTube again started recommending to me channels of people who died of cancer. I looked at a clip of a man just a few years my senior where he was describing the symptoms that in his view should have made him go see a doctor earlier, because maybe then his pancreatic cancer wouldn't have been fatal. Truth be told they wouldn't raise any red flags if I had them. Only thing that I'm doing differently is having blood tests done on an annual basis, but those only show anything when e.g. the cancer has spread to the liver, which is typically too late anyway. It's an incredibly insidious disease, and if the tumor is growing on the wrong end of the organ, it won't give any symptoms whatsoever.
- bluGill 8mo agoThat is the problem with symptoms in general. Most people who go to the hospital with "chest pain" are not having a heart attack - but it is still the best symptom we have and so emergency rooms "waste" a lot of time one people who have nothing wrong. Or more likely they just have a mild constipation case (look up constipation, and then look up the individual symptoms - most of them are also symptoms of GET TO THE ER NOW type things)
- TaupeRanger 8mo agoAnd they shouldn’t raise red flags. 99.9% of the symptoms any individual experiences in their life are not life threatening. If you got scans and interventions at every symptom, you’d end up in debt and with iatrogenic harms. Until we can get more accurate data from our bodies more easily, this is the reality. The good news: there’s so much room for innovation and progress in medicine.
- tjpnz 8mo ago>Only thing that I'm doing differently is having blood tests done on an annual basis Tumor markers? Did one once because it was a cheap add on to my annual medical. Which then led to a rather more expensive MRI (lucky for me it wasn't cancer). Genuinely curious if those tests have helped anyone here as a preventative measure.
- Tade0 8mo ago
- wolfi1 8mo agoif that holds true in humans that would be a huge win. but it would be interesting at which stage those drugs still help. btw, it is said Chris Rea was diagnosed with pancreatic cancer at the age of 33, he died last year at he age of 74. it would be interesting to know what circumstance helped him to fight the cancer for such a long time
- deleted 8mo ago[deleted]
- bitwize 8mo agoAnybody read that as "Dugtrio found to block tumour resistance..."? "Here we describe peptides secreted as part of the Diglett evolution process, that have been found to disrupt oncocyte metabolism in vitro..."
- wormius 8mo agoAm I misunderstanding the headline? Is the word "block" now meaning "enhance" instead of "stop"? I would think based on the text of the article that it enhances resistance. Or are tumors necessary to stop cancer growth (even though it is cancer growth?)
- ekianjo 8mo agoAt usual baity headline. It's in rat, it's on a tumor model, so there is a good chance it's like the other thousands mice studies that do not replicate on humans
- pvaldes 8mo agoThis should be seen as a warning of how much time and efforts and money and stability are required to cultivate a discovery that could have never happened. Spanish researcher from Madrid. Hired by US on a grant. Worked hard and became director of the Oncology department on the NCI on Maryland. Somebody on the Spanish government decided to bet strong on him and recover it for Spanish Cancer research. A specific customised job offer was created for him. Politicians came and go; some are sensitive about science, other not so much. Some promises were never fulfilled, and he was about to quit and migrate again until private companies stepped on the scene with the resources needed and the will to allocate those resources. Money well spent, that was about to never find his target. Nobel prizes were created exactly for this kind of humble, serious, zero-nonsense, zero-drama, all-work scientists. The question here is: how much "Barbacids" quit US in the last year? Scientists aren't stupid. Everybody is aware that Barbacid in US today would have being harassed just for speaking Spanish and having a scarred face. All points that US is bleeding talent at a level never seen in their history.
- quentindanjou 8mo agoAs we are always starting with mice, I am wondering if there are some drug that could work on humans but not on mice.
- shusaku 8mo agoAbsolutely there is, which is why they haven’t genetically modify the mice for useful experiments.
- deleted 8mo ago[deleted]
- arjun_krishna1 8mo ago[flagged]
- giwook 8mo agoI read this as "Dugtrio found to block tumour resistance". As in the Pokemon.
- ltbarcly3 8mo agoI wonder what it would take to get people to stop up-voting animal model cancer cures? Guys, these are a dime a dozen and you never hear about them again. All like 6 stories from this site on hn are some cancer cure that went nowhere.
- pointbob 8mo ago[dead]