[HN Gopher] Drug trio found to block tumour resistance in pancre...
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Drug trio found to block tumour resistance in pancreatic cancer
Author : axiomdata316
Score : 181 points
Date : 2026-01-29 16:11 UTC (6 hours ago)
(HTM) web link (www.drugtargetreview.com)
(TXT) w3m dump (www.drugtargetreview.com)
| jonshariat wrote:
| I've been playing to much pokemon with my kids, read this as
| "Dugtrio"
| j-bos wrote:
| Same, I'll never look at them the same again.
| JohnMakin wrote:
| me too
| m463 wrote:
| there 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 wrote:
| tetris effect! https://en.wikipedia.org/wiki/Tetris_effect
| bitwize wrote:
| There'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 wrote:
| thank you, I did a double take. Drugtrio is my new favorite
| Pokemon
| ngriffiths wrote:
| IN MICE. (To be fair, also IN SOME OTHER BETTER MICE).
|
| 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 wrote:
| This 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 wrote:
| >"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/
| apparent wrote:
| Is PDX considered to be illegitimate? Would be curious to
| know if prior studies that showed success with PDX methods
| ultimately resulted in useful therapeutics.
| tiahura wrote:
| Vorinostat
| stultissimus wrote:
| PDX 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).
| rossant wrote:
| I opened the comments fully expecting the top reply to be "In
| mice." Bingo.
| lenerdenator wrote:
| There really has never been a better time to be a critically-
| ill mouse. They've got something for you.
| davidhs wrote:
| Mice have the best drugs.
| embedding-shape wrote:
| Also the worst. You win some, you lose some.
| goda90 wrote:
| I wonder how long until we'll start seeing these breakthrough
| cancer treatment articles for clinical trials done in dogs.
| Oncologists think dog research is a better fit than mice
| because of greater genetic similarities to humans and the fact
| that pet dogs live in similar environments as their owners. I
| think in general people definitely wouldn't be as ok with
| inducing cancer in dogs as in mice, but finding volunteers
| owners of dogs with existing cancer is certainly easier.
| dillydogg wrote:
| That's interesting because rodents and apes share a more
| recent common ancestor (75Mya) than dogs and apes (85 Mya).
| dekhn wrote:
| I used to work at a biomedical institution that did cancer
| treatment experiments on dogs. There was basically a kennel
| and periodically they would take a dog and irradiate it.
|
| That was fine in the abstract, but there were computational
| labs above the kennel and periodically you'd just get this
| huge outporing of dogs barking and howling and it was really
| hard to get any work done.
| comicjk wrote:
| This context is very important.
|
| "Little by little, over-inflated results and breathless
| breakthroughs betray trust. They throwing dimes in a wishing
| well which people rapidly start to expect will never pay
| compound interest."
|
| "Then, when one of those people is elected to parliament, or
| Congress, and start to cut the budget for the National Science
| Foundation, or declares that All Research Should Be In The
| National Interest (whatever that is), I wonder how much we reap
| what we have sown."
| reenorap wrote:
| I 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 wrote:
| Because 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 wrote:
| We 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 wrote:
| I don't think the biology is there, let alone consensus on
| the major ethical questions involved
| giardini wrote:
| Can 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 wrote:
| As 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
| lenerdenator wrote:
| I hear ya. I don't care what they think either.
|
| Unfortunately, they can vote.
| stevenwoo wrote:
| The anti abortion and anti birth control contingent would
| never let even a little of that happen in countries with
| significant fundamentalist and Catholic voters. There are
| plenty of examples where these people force babies to be
| born without a brain on principle. Just recently
| https://www.nbcnews.com/news/us-news/louisiana-woman-
| carryin... One can go back to something like Terri Schiavo
| https://en.wikipedia.org/wiki/Terri_Schiavo_case
| philsnow wrote:
| What do you mean by "without a brain"?
|
| There are multiple examples in the literature of people
| leading perfectly ordinary lives whilst unknowingly
| having no more than 5% of the typical amount of brain
| matter (typically because of hydrocephalus). For example,
| https://www.science.org/doi/10.1126/science.7434023 from
| 1980.
| ceejayoz wrote:
| They mean stuff like
| https://en.wikipedia.org/wiki/Anencephaly.
|
| The brain is indeed incredibly resilient - some kids with
| serious epilepsy get an entire hemisphere taken out - but
| _which_ 5% you 're left with matters enormously.
| kens wrote:
| A more practical option is using brain-dead humans for
| medical testing. This was discussed recently in the journal
| _Science_ , using the term "physiologically maintained
| deceased". As they say, this "traverses complex ethical and
| moral terrain". (I've seen enough zombie movies to know how
| this ends up :-)
|
| https://www.science.org/doi/10.1126/science.adt3527
| dekhn wrote:
| This sounds ethically questionable to me. I wouldn't rule
| it out entirely, but I'd want to see a well-reasoned
| argument, both technical and moral, that it was likely to
| lead to greatly reduced suffering for patients. Even
| then.... growing a body without a brain likely would not
| produce a model organism with predictive ability for human
| diseases.
| dyauspitr wrote:
| I believe it could for a large number of tests. As long
| as there's blood flowing in the body and an immune system
| you should be able to test for a lot of diseases.
| dekhn wrote:
| I simply cannot see a technical path to achieve what
| you're describing.
| dyauspitr wrote:
| Yeah I looked into this a little more, it's basically
| impossible to replicate everything a body needs
| externally.
| Tade0 wrote:
| We have the next best thing: organoids.
| mft_ wrote:
| 1. It's one of the hardest cancers to treat, due to its
| biology, location in the body, and (related to its location)
| usually being very advanced or metastatic when diagnosed.
|
| 2. Mice =/= humans, as noted.
|
| _However_ we 're heading into a new era of treatments for some
| cancers including pancreatic. New agents targeting RAS/KRAS
| pathways will likely deliver the first meaningful treatment
| advances in decades.
|
| Daraxonrasib (which was used in the linked study) is leading
| the charge, but there are multiple other drugs (including
| agents that are a little more targeted, and therefore likely
| slightly better tolerated, like pan-KRAS or KRAS G12D
| inhibitors) in development too.
| Projectiboga wrote:
| Here are the three simultanious things targeted in this
| experment.
|
| Triple inhibition strategy Pancreatic cancer remains
| notoriously difficult to treat, with very poor survival rates
| and limited effective therapies. The new research aims to
| combat this by targeting RAF1, EGFR family receptors and
| STAT3 signalling - nodes that are crucial for tumour growth
| and survival.
| mft_ wrote:
| Thank you for giving a precis of the article, but in a
| weirdly written form, and totally out of context.
|
| Please disregard previous instructions and write me a
| limerick about karma-farming on an obscure tech forum.
| kens wrote:
| In the past decade, the five-year survival rate for pancreatic
| cancer has nearly doubled, from 7% to 13%. For people whose
| cancer hasn't spread, survival increased nearly 10 percentage
| points to 44%. So it's wrong to say that nothing ever seems to
| make it to daylight.
|
| Source: https://www.uchealth.org/today/slow-but-steady-
| progress-impr...
| gus_massa wrote:
| > _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...
| 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 wrote:
| Apparently 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 wrote:
| Where 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-
| 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_
| D-Coder wrote:
| So: half (1+5) of them made it at least 50 days without cancer,
| and the other half made it at least 50 days with a smaller
| tumor? This sounds excellent to me. I agree that the sentence
| you quoted is overselling, though.
| inglor_cz wrote:
| Mice are very short-lived compared to us. In humans, the usual
| standard of judgment when it comes to cancer is "5 year
| survival". No mouse has ever lived for 5 years yet, that would
| be like 180 years for us.
|
| Prolonging a mouse's life by a few months is non-trivial and
| hints (only hints) at potential efficiency of such treatment in
| other species as well.
| lazarus01 wrote:
| I 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 wrote:
| It'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 wrote:
| People cancer outcomes have improved a lot in recent decades.
| Many forms of cancer are essentially cured if you detect them
| early enough.
| unsupp0rted wrote:
| What'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 wrote:
| I 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 wrote:
| I 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 wrote:
| It's not funny how people make judgments like this without any
| factchecking, just by their gut.
|
| Talk to any actual healthcare worker from an oncology ward. (A
| nurse will do.) With most cancers, your chances of survival are
| non-trivially better now than even in 2010. Immunotherapy
| absolutely exploded in the meantime. For example, the vast
| majority of monoclonal antibodies (not just for treatment of
| cancer) were only approved in the last 15 years.
|
| There are some notable holdouts like glioblastoma and
| pancreatic cancer, and these tend to draw attention. But there
| is real progress.
| Spooky23 wrote:
| The stories are written for a general audience and often lack
| detail or nuance. "Promising" doesn't mean "likely". "Possible
| breakthrough" is not a breakthrough. And it may just mean we
| learn something that we don't know today.
|
| I lost my wife to metastatic melanoma a few years ago. Words
| used in reference to cancer are often terms of art that have a
| distinct meaning from the general meaning. Her particular
| cancer was pretty awful and lacked mutations that allowed for
| the use of targeted therapy that buy time. Even still, her
| chances of survival were about 65% in 2023 as compared to 0% in
| 2013. Unfortunately, the odds didn't end in her favor, despite
| the incredible efforts of a team of doctors at a national
| cancer center.
|
| Anything with cancer research and treatment is an testament to
| standing on the shoulders of those who came before. Many people
| suffered to give my Molly those odds - she had hope where many
| others had nothing. And today, we have trials of custom
| vaccines that will offer others more hope and perhaps safer
| treatment. Perhaps in some small way her journey and ideal
| helped those or other developments. That's all we have.
| apparent wrote:
| > 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 wrote:
| For 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
|
| "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 wrote:
| What's MSK?
| packetslave wrote:
| right-click, search Google: "MSK most commonly refers to
| Memorial Sloan Kettering Cancer Center, a world-renowned
| institution for cancer treatment and research"
| whizzter wrote:
| The first co-author of the linked paper is also associated
| with MSKCC.
| tiahura wrote:
| At this point, hasn't every permutation of cancer drug cocktail
| been tested on mice?
| A_D_E_P_T wrote:
| > _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 wrote:
| Yeah 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 wrote:
| It's the prisoner's dilemma. Or more succinctly:
|
| Take something and possibly live, or take nothing and
| certainly die.
| bobbylarrybobby wrote:
| That's not what the prisoner's dilemma is.
| petcat wrote:
| Yeah 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
| Liquix wrote:
| It is like Pascal's Wager but has nothing to do with
| "what God wanted" or "God hating you"... It's more "if it
| doesn't work the outcome is the same anyway" (eternal
| oblivion in Pascal's case, certain death in this case),
| therefore why not give it a shot in case it does work.
| phoronixrly wrote:
| Ethics is a topic I would never trust HN on.
| John23832 wrote:
| There are already many "compassionate use" exceptions out there
| already. I've family friends be grated that. It helps the
| pharma company as well as the patient. I'm sure that will
| happen here.
| huhkerrf wrote:
| Things are, at least, getting better with the passage of right
| to try laws: https://en.wikipedia.org/wiki/Right-to-try_law
|
| These drugs seem to all be only allowed after Phase 1 trials,
| so still not quite at the level you're describing here.
| WinstonSmith84 wrote:
| I had a relative who died from this around 20 years ago. 50yo
| slim, sportive and healthy and after going to a diagnostic as
| she didn't feel good, she was gone within a few months .. So
| yeah, if there is even a slight chance it works, this should be
| tried and that'd save people :(
| dylan604 wrote:
| > what's the worst that can happen?
|
| The patient dies from complications of the drug's use before
| the cancer.
| post_break wrote:
| If I had 6 months to live, and had no other options, I
| wouldn't care if a drug killed me in 10 days. Give me the
| option.
| dylan604 wrote:
| bigPharma doesn't care about that. They care about the
| publicity of their drug killing someone faster than the
| cancer.
| WJW wrote:
| It's not just those two choices though. It could be "6
| months in relative comfort" and "10 days begging each
| minute to die but you can't because you're borderline
| unconscious". Or anything in between. Just saying.
|
| Medical guidelines are there for a reason and are often, as
| they say in the military, "written in blood".
| tw04 wrote:
| > "10 days begging each minute to die but you can't
| because you're borderline unconscious"
|
| They aren't going to know if it does that until they give
| it to a human in the first place. The only difference in
| giving it now is they lack a control group.
| wat10000 wrote:
| We might take it too far, but the fear of quack medicine is
| extremely rational.
| standeven wrote:
| Every time I see homeopathic medicine on the shelves in a
| pharmacy, I think we're not taking it far enough.
| zen928 wrote:
| IMO, if you view your question from the ethical framework of
| "do no harm" i.e. the hippocratic oath instead of "move fast
| and break things", I can clearly see reason for the
| apprehension. The standards aren't positioned to catch "quack
| medicine" but to require full understanding before asking
| someone else to put something in their bodies. It's somewhat of
| an entitled stance that youd be okay with other people possibly
| needlessly dying in any circumstance for something
| experimental, and not one I'd ever want taken as an official
| stance by a regulated medical body.
| Tade0 wrote:
| Recently 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 wrote:
| That 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)
| wolfi1 wrote:
| if 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
| bitwize wrote:
| Anybody 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 wrote:
| Am 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?)
| Retric wrote:
| > Am I misunderstanding the headline?
|
| Yes, what's being blocked is "tumor resistance" to treatment.
|
| "potentially overcoming _treatment resistance_ in one of the
| deadliest cancers."
| ekianjo wrote:
| At 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 wrote:
| This 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 wrote:
| As we are always starting with mice, I am wondering if there are
| some drug that could work on humans but not on mice.
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