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epistasis 2 days ago [-]
Metastatic pancreatic cancer is the first indication for this class of RAS-inhibitor, but it certainly won't be the last, and it seems certain that there will be many many more cancers where this drug gets approved. There are mutations to activate KRAS in a substantial fraction of cancers across many organs, and but it's been such a hard protein to target with a drug that even decades ago I was told it was "undruggable."
What's going on with this new drug is a somewhat novel mechanism: instead of gumming up the enzymatic action of the protein, it acts as a glue between KRAS and a common "helper" protein, that then mucks up the RAS signalling. This sort of molecular glue mechanism has had a few examples built up over the past decade, but this is a really knock-it-out-of-the-park drug. Really amazing, and because of it lots of people are focusing lots of effort on how to discover more molecular glues.
pfdietz 2 days ago [-]
One downer about this drug is the absolutely horrific side effects, like "your skin feels like you've been dipped in acid" kind of horrific. Still, pancreatic cancer is just that bad, so maybe that's worthwhile.
epistasis 2 days ago [-]
Yes, the side effects were very extreme. As time goes on, I'm optimistic that management of the side effects will improve, and outcomes will improve along with that too. Much like chemotherapy, this type of treatment affects a lot of non-cancer cells too.
jmcgough 2 days ago [-]
It's such a big deal to get a working RAS drug. Pharma companies will be pursuing additional drugs of the same class after this - much easier to be the second than the first. I think over the next few years we may see improvements on this, or better figure out how to use it and manage side effects. Very exciting!
jquery 23 hours ago [-]
The alternative is chemotherapy which is even nastier, on average.
pfdietz 13 hours ago [-]
I'm not sure conventional chemo actually is nastier than this drug. It sounded really bad. Conventional chemo is less effective here, though.
1 days ago [-]
MarceliusK 1 days ago [-]
If molecular glues keep working like this, I wonder how many other "undruggable" targets are really just targets we've been trying to attack in the wrong way
jmcharnes 2 days ago [-]
My sister was diagnosed with pancreatic cancer in October (48 years old) and died in June from it.
I'm glad to see a drug like this developed for people suffering from pancreatic cancer. I don't wish what my sister went through on anyone.
Damn if I don't wish it had come a little sooner.
mwigdahl 2 days ago [-]
My father-in-law died of pancreatic cancer three months after diagnosis.
It is a horrible disease, not least of which because it’s difficult to diagnose. By the time they get a clear bead on it, in many cases, it’s stage four and already ravaging your system.
I’m very sorry for you and your family’s loss. And I hope this drug makes it so a lot fewer people have to go through this in the future.
MarceliusK 1 days ago [-]
I'm really sorry for your loss. There's not much to say to something like that except that I hope this treatment came too late for fewer people than it did for your sister
freediddy 2 days ago [-]
I'm very sorry for your sister's death. My friend's dad was diagnosed with pancreatic cancer out of the blue and died within 6 weeks. It terrifies the fuck out of me because there's nothing you can do to detect it or fight it. Hopefully this drug helps people get cured of it.
e40 1 days ago [-]
Sorry for your loss. My best friend died 3 months after diagnosis from pancreatic cancer.
pfdietz 2 days ago [-]
My mother died of it less than two weeks after the diagnosis was confirmed by biopsy. On the other hand, I knew a guy at work who survived more than five years with it; this was so unusual there was an advocacy group that used him as a kind of poster child of hope. He looked just terrible though.
jghn 2 days ago [-]
a lot depends on the exact diagnosis, both stage and the specific kind of pancreatic cancer
2OEH8eoCRo0 2 days ago [-]
Sorry for your loss. My mémère passed recently from it. It's a terrible illness and I'm glad that others can have more time.
seizethecheese 2 days ago [-]
mémère Is French for grandmother, for other readers, since I looked it up.
Spooky23 1 days ago [-]
I’m terribly sorry. I lost my wife to metastatic melanoma.
It’s hard as in 2013, the treatment was “get your affairs in order”. In 2023 her chances were 60/40 due to immunotherapy. Unfortunately she ended up on the wrong side of those odds. Today, the Moderna trials are improving those outcomes significantly, and I think that cancer will be fully treatable in a decade or so.
It’s almost a miracle… but the road to “better” is built on the shoulders of those who came before. I find it both a source of hope and of regret for what could have been.
jmcharnes 1 days ago [-]
I'm so, so sorry you lost your wife to cancer. Cancer is cruel, in so many ways.
> but the road to “better” is built on the shoulders of those who came before
This really resonates with me. I appreciate you sharing it. I'll be sharing it with my family, too.
hentrep 2 days ago [-]
Beyond the data, this approval is notable for the speed from FDA acceptance of their new drug application (NDA) to FDA approval - just over a month. Compare this to the typical 8-12 month timelines we've historically seen for priority and standard reviews, respectively. This was enabled by the FDA's CNPV Pilot Program [0]
Seriously? So for example the covid vaccine should have been approved in 1 month based on the crisis response or because mRNA approach is transformative, or if it could be made in the US. I feel so much safer knowing a reckless FDA won't be a problem now.
seizethecheese 2 days ago [-]
I’m trying to understand your point. This drug is for people with metastasized cancer. I’m comfortable with fast tracking it, because what’s exactly the harm of letting desperate people try something that seems likely to help a lot?
Also, the risk profile is sort of the inverse of a covid vaccine where everyone was supposed to take it.
norbertsboat 2 days ago [-]
The FDA article lists 5 reasons the pilot of the pilot is only for the non controversial one that is not even listed in a way that maximizes its risk/benefit requirements.
hentrep 2 days ago [-]
Comparing the acceleration of FDA approvals for non-contagious terminal diseases like PDAC to development of COVID vaccines is flawed on so many levels. You make it sound as though this was just cooked up in some desert meth lab RV over a weekend, and the FDA just rubber-stamped after a cursory glance at the data. The Phase 1/2 study first exploring daraxonrasib (RMC-6236) was posted on clinicaltrials.gov in May 2022; this trial enrolled 754 patients [0]. The RASolute 302 study this approval is based on was first posted to clinicaltrials.gov in October 2024; this trial enrolled 500 patients [1]. Nevermind the years of preclinical discovery and translational work that had to precede human studies.
As you can see from the control arm showing 6.7mo of survival on standard of care chemotherapy, these patients have a very poor prognosis. Is this a cure? No. Does it buy time to see your child graduate, get married, or give birth? Quite possibly.
If you ever have the opportunity to work behind the scenes within the pharma industry and/or FDA, you'd be astonished that anything ever gets approved with all the red tape and complexity along the way. Medicine is not software - it operates within the black box of human biology which is incredibly nuanced from patient to patient.
Like many who have shared personal stories in this thread, I've lost friends to PDAC. It is a terrible disease often driven by a mutated oncogene (KRAS). Many cancers have KRAS-driven subtypes (lung, colorectal, low-grade serous ovarian, etc). The clinical platform and pipeline at RevMed has potential to address many other cancers. They have next-gen RAS agents that could be even more impactful.
For those curious, RevMed posted a solid summary of the approval on their IR site [2]
Good post but the whole "buy time to see your child graduate, get married or give birth" trope is quite frankly very annoying.
Older people have more going on, and more reasons to live, than whatever the next generations are up to. Even if we have children.
I had curative (hopefully, presumably) kidney cancer surgery 11 years ago. So far I've enjoyed travelling, socializing, working, coding, chess and other hobbies in the extra time I've been granted and I hope for decades more time to enjoy life. I don't have children. never aspired to it.
Sorry for the rant!
mlyle 1 days ago [-]
I have kids.
I also travel, socialize, work, code, play video games, solve puzzles, etc. Love all that shit.
I'd be sad to "miss" some novels, or to never see the Ocarina remake, etc. Or just the time I spend piddling around with things.
But I think if I was about to die and an advance bought me a few months of moderate quality life, it'd mostly be about seeing my kids cross milestones. I don't imagine I'd spend nearly as much time cranking through those things.
billforsternz 1 days ago [-]
Understood. No doubt I would be similarly inclined if I'd gone down that path in life. My beef is that I feel this is a trope that gets rolled out without question, and it doesn't even bother paying lip service to the diversity of human experience.
I feel similarly whenever I hear about someone expressing empathy with someone, but apparently only after realizing they are someone's daughter/brother/sister/mother whatever type of relative. What's that about? I feel empathy for any innocent victim, they're human, they're living a life, maybe a very enjoyable life even if they don't have a single relative.
forestrywat 1 days ago [-]
It's a trope for a reason. Having kids does shit to your brain and breaks it in a bunch of ways you cannot anticipate. For better and for worse.
norbertsboat 1 days ago [-]
Read the stuff you link to. The FDA article on their criteria says nothing about it needing to be for terminal cancer (is high cholesterol terminal?) Make anthrax hemroid creme in the US and it meets the criteria of the pilot. You should stop falling for scams like being presented with a first result of a pilot that is an improvement and not reading that the pilot itself was created for the other 4 scam cases.
dmschulman 2 days ago [-]
My dad was diagnosed with pancreatic cancer in December 2019 and thankfully caught wind of it in its early stages due to an eagle-eyed nurse going over some routine blood work and noting his liver numbers were off, he should talk to the doctor.
You can imagine how hard it was to be sick in the early days of COVID, much less have to go to the hospital on a regular basis to receive chemotherapy for hours on end. Our family was lucky that he responded well to treatment at least and we had a few extra years with him before he passed away in late 2023.
Cancer is a terrible thing but pancreatic cancer is especially horrible due to the difficulty in detection when you're in otherwise good health. The fact that intense medical research into retrovirals has yielded something so significant as the RAS-inhibitor is nothing short of miraculous.
mstank 2 days ago [-]
My mom was diagnosed with borderline stage-4 pancreatic cancer. Fortunately she had an aggressive surgeon willing to do a Whipple procedure, and survived almost 4 years after a 4-6 month prognosis.
We were incredibly lucky to even have that time with her. Pancreatic is one of the worst cancers someone can get — both for survival and quality of life.
I’m very happy to see that we’re finally making meaningful progress on treatment.
datakan 2 days ago [-]
My dad passed in 2020 from pancreatic cancer. He'd been to the doctor several times complaining about issues and all they would do is send him home with laxatives. Eventually it got bad enough my mom ran him to the ER when they found the cancer which had progressed into its final stages already. He was dead less than a month later.
Similar story with a guy I worked with. He went home sick one day. A few days later our boss told us he was sick and had pancreatic cancer. He came into the office to say goodbye to us a few weeks later and then died about 10 days after that.
Fuck cancer
canucker2016 2 days ago [-]
Matt Bencke's pancreatic cancer story has stuck with me.
First sign in May, followed by several doctor visits which treat the symptoms.
In late July, he heads to the ER. Multiple tests later, he and his wife get the diagnosis.
FWIW it's commonly the case with cancers of abdominal organs: stomach, pancreas, liver, kidney, etc. These cancers are frequently not diagnosed until at an advanced stage. Symptoms tend to be nonspecific, overlap with ubiquitous conditions like constipation, gastritis.
A goal of research is improving early detection of these cancers but it's an uphill battle. It's difficult to increase providers' "index of suspicion" of seemingly "minor" complaints.
yepyeppers 2 days ago [-]
That’s a generalization, pancreatic cancer is often extremely lethal, depending on the type and case the survival rate can be as or more grim than glioma. Bowel and urinary cancers including kidney cancer are often very treatable and survivable when discovered due to symptoms. I don’t think it’s helpful to group all abdominal cancers as being uniquely or especially bad or late discovered. Likewise for the particularly aggressive or advanced cancers these types of announcements and trials rarely translate to major changes in prognosis. More typical if there is any positive result it looks like additional weeks or at best months of aggressive treatments rather than significant ”cure” rates.
HedonicEscal8r 2 days ago [-]
It can be disappointing to see that even a successful drug, like this one, is "only" extending life expectancy from 6.7 months to 13.2. But this is what the first steps towards a cure look like.
Childhood leukemia used to be overwhelmingly fatal, and early chemotherapy trials also only managed a couple months of remission. Researchers were even criticized for subjecting patients to harsh side effects to no apparent benefit. But thanks to that research, most patients are now cured; per capita death rates from childhood leukemia are down 14x from the 1950s, mostly driven by improved treatment.
Daraxonrasib is an incredible invention on a technical level, and a meaningful step forwards in the treatment of many cancers. We'll need a couple more equally incredible inventions to be able to cure pancreatic cancer.
freediddy 2 days ago [-]
Moderna is testing an mRNA vaccine that might be useful against bladder and kidney cancers. Hopefully the same technology can be applied to pancreatic and liver cancers. Fingers crossed.
HedonicEscal8r 13 hours ago [-]
mRNA vaccines are being studied for pancreatic cancer. To quote a post I wrote in April:
> First, the personalized mRNA vaccine autogene cevumeran, developed by BioNTech and Genentech, just reported 6-year follow-up results from their Phase 1 clinical trial. 16 patients were treated, 8 were responders (showed signs of immune reaction to vaccine), 8 were non-responders.
> 7/8 responders (87.5%) survived 6 years after surgery, 2/8 nonresponders survived (25%).
> The most important result in this small trial is that vaccine response is strongly correlated with better outcomes. But for context, the trial was restricted to patients with operable pancreatic cancer. Patients diagnosed with stage 1 or 2 pancreatic cancer have a 5-year survival rate of 12%. Patients who get their pancreatic cancer surgically removed have a 5-year post-surgery survival rate of 20%. This makes the overall 6-year post-surgery survival rate of 56% among the 16 trial patients pretty impressive. Keep in mind that the trial patients may have been healthier than average for other reasons, and small n is small n, so we shouldn't be too hasty until we see Phase 2 and 3 data.
Still early, unfortunately, so it will be a while before we see more updates.
greenowl 2 days ago [-]
We are able to early detect these cancers right now with routine targeted imaging. Perhaps we should be working to solve or improve on the drawbacks associated with doing this, some of which are:
CT scans emit ionizing radiation.
MRI contrast can buildup and be retained in the body over repeated administrations.
The scans can produce false positives, surface benign abnormalities which result in a wild goose chase, cause severe patient anxiety and healthcare burden, and result in over-treatment.
And of course doing this on a whole population level is not cost or time effective.
freediddy 2 days ago [-]
> And of course doing this on a whole population level is not cost or time effective.
It will never be cost or time effective if we never try. I'm paying out of pocket every year for an MRI scan, this was my second year this past year.
jr3592 2 days ago [-]
Absolutely terrible. As human beings, we should be prioritizing solving these kinds of problems. I don't think we need to live forever, but a graceful ending later in life remains an objective we haven't fully realized for everyone.
yepyeppers 2 days ago [-]
We do. There’s something like half a billion dollars spent on pancreatic cancer research annually in the United States alone. It’s a giant money pit and that’s created an enormous body of research, increased understanding of the biology of the cancer and just how insidious it is, and funded the careers of thousands of scientists, technicians, academics and administrators, but very little of all this translates into better treatment outcomes. There’s no evidence than just pouring more money into cancer research is going to give us a miracle cure. There are competing priorities starved for funding to that we know can use meaningful help. Not incidentally some of those include financial aid, medical care and quality of life assistance for the actual patients and their families, as well as prevention.
snowwrestler 1 days ago [-]
> There’s no evidence than just pouring more money into cancer research is going to give us a miracle cure.
The HPV vaccine will almost entirely wipe out cervical cancer: not by curing it, but preventing it entirely. Not sure if that meets your “miracle” standard, but it’s a totally unreasonable standard to apply to scientific research. By definition, a miracle is something that is not physically possible.
Research seems expensive, yes. You have to work in every possible direction, fumbling in the dark metaphorically, because you don’t know the answers yet. It’s a lot messier than giving a hungry person a meal. But hundreds of years of research have made that meal way more abundant and less expensive…
In the grand scope of the country, we spend quite small amounts on research. The U.S. GDP generates half a billion dollars in less than 10 minutes, for example. It’s less than what we spend on takeout coffee.
jr3592 22 hours ago [-]
Even better point. Thank you!
jr3592 2 days ago [-]
good point
wvh 1 days ago [-]
My aunt died of this last year. It took all of three months. That has given some food for thought in my family over what the most humane and merciful way to die is; 5 minutes and a heart attack, three months and this, or several years in other forms of cancer and tumours.
Ignoring the pain aspect of the disease, three months seems not to be a bad time to come to grips, say your goodbyes, tie up loose ends but not prolong suffering indefinitely and waste away.
Also, hail to healthcare systems that facilitate legal euthanasia.
MarceliusK 1 days ago [-]
Pancreatic cancer is one of those diseases where I've gotten used to reading depressing numbers, so seeing 13.2 months vs 6.7 months actually made me stop for a second
Alien1Being 1 days ago [-]
Not a nice disease to get. Ranks up there with glioblastoma multiforme, advanced oesophageal cancer and advanced duodenal cancer.
I am aggressive and investigate aggressively to detect pancreatic cancer early. One even had a Whipple procedure (pancreaticoduodenectomy ), since I detected it so early.
Despite that, the longest anyone I diagnosed has lived has only been 8 months.
Sad, they were all nice people.
jquery 23 hours ago [-]
> glioblastoma multiforme
Killed my dad the same year he retired. Really stuck with me about how important living for today is.
Wonnk13 1 days ago [-]
stage 4 colon cancer here... Pancreatic cancer is obviously a _very_ different disease, but when i was diagnosed just about a decade ago the conventional wisdom was that KRAS was basically undruggable. I'm KRAS 12D and very excited for future.
No it's not a cure, but this drug is the difference between someone's mother or father making it to one more Christmas, or Birthday, or other life milestone.
botro 2 days ago [-]
My father in law was diagnosed with stage 4 pancreatic cancer that's spread to his lungs about a month ago. This news today raised my wife's hopes immensely and had them immediately doused after hearing the oncologist say that although the drug is approved it will take months before they are able to prescribe it.
Father in law started chemo a few weeks ago and his condition deteriorated quickly, he's been at the hospital since; switching between ICU and general care. His abdomen fills up with fluid, around 6 liters every 5 days, draining the fluid plunges his blood pressure and he end up in ICU. They supply Albumin until blood pressure stabilizes and send him back to general. Only after the first chemo session the oncologists have stopped the treatment saying he's no longer eligible for chemo because of his over all health.
We're lucky enough to live an hour away from Johns Hopkins (though that's not the hospital he's currently at) and had an appointment scheduled but had to cancel since he's unable to walk.
The oncologist mentioned that daraxonrasib was available as an option when he first started chemo, but said he would only be eligible for it after trying chemo, so we know the drug is available.
Are there any tips from HN on how we can approach getting this medicine for my father in law?
I would suggest you have your physician submit a Expanded access request immediately, because the same page says that they will close this program after FDA approval as they transition to commercial use, but the timeline for that is unclear.
botro 2 days ago [-]
Thank you for sharing.
octaane 2 days ago [-]
Ask the oncologist directly. Also, try contacting Revolution Medicines directly (the manufacturer), and/or go through their early access page: https://www.revmed.com/expanded-access-policy/
botro 2 days ago [-]
Thank you for sharing, the oncologists are saying that at this point in the diseases progression the same things that disqualify him from getting chemo also disqualify him from this drug. That in his current state it would do more harm.
I hope many others are helped by daraxonrasib, the key factor seems to be how early the cancer is detected, because it is an extremely fast acting disease.
woadwarrior01 1 days ago [-]
This would've likely saved Steve Jobs, had it arrived 15 years earlier.
catoc 1 days ago [-]
No, this is for metastatic pancreatic adenocarcinoma, not what he had
astura 1 days ago [-]
No it wouldn't have. This treatment is for pancreatic adenocarcinoma.
Steve Jobs had pancreatic neuroendocrine tumor, which is a rare form of pancreatic cancer.
Same organ, but fundamentally different diseases.
Pancreatic neuroendocrine tumor is usually quite treatable, but Steve Jobs delayed surgery for almost a year to try to beat his cancer "naturally" - with a fruit diet, herbs, and acupuncture. Were he had gotten the surgery right away, there's a very good chance the cancer wouldn't have spread and he would be alive today.
Beyond that, from tfa
>Rasonque improved median overall survival to 13.2 months compared to 6.7 months for standard chemotherapy.
inglor_cz 1 days ago [-]
Jobs was lucky enough to have a completely different, very treatable type of pancreatic cancer, and unlucky enough to believe in crackpot treatments more than actual science.
silverFork 2 days ago [-]
The therapy does not provide a cure. Just prolongs lives for only few more months, unfortunately .
matthewsjess 2 days ago [-]
Fantastic news. Research on Metastatic treatments has been underfunded. Yet immunotherapy and other treatments are showing amazing promise.
octaane 2 days ago [-]
I would argue that it is not underfunded, as most big pharma companies with oncology products have dumped enormous amounts of money into research pipelines and clinical trials. Immunotherapies like nivolumab or ipilimumab or pembrolizumab have varying (but often very decent) efficacy data for metastatic disease across tumor types.
chilldsgn 1 days ago [-]
Someone I love dearly passed two weeks ago from this awful cancer. She was on a trial for this drug, but it was ineffective, sadly. I can't stop crying. This is a horrible disease and I am so glad there are developments being made in this to extend people's lives, possibly even save them.
Fuck cancer.
dyauspitr 2 days ago [-]
We’re nowhere close to it, but if we actually solve the vast majority of cancers, we will have taken several steps towards a true utopia
GrinningFool 2 days ago [-]
Assuming access to those solutions for everyone, sure.
SeifHashish 2 days ago [-]
thats great news !
mchusma 1 days ago [-]
FDA is just too slow. Whole I’d like to do more radical reform, at a minimum this stupid long wait should be tossed. If someone hits a target endpoint auto approval pending further review or something
Remember in COVID when results. Came in and they took a month to schedule the meeting?
nottorp 1 days ago [-]
Self approval? Like Boeing?
canucker2016 1 days ago [-]
Is Boeing terminally ill? </rhetorical>
Jake Seliger, HNer, jseliger - https://news.ycombinator.com/user?id=jseliger, who died a couple of years ago, had exhausted the current standards of treatment for head-neck cancer. Drugs available through clinical trials were his last option.
But the workflow to access drugs via clinical trial is terrible. Directions/Instructions aren't documented. Unwritten limitations and optimizations.
Jake and his wife documented his path through the process.
"The biggest bottleneck in the clinical trial system is recruitment and retention. It’s hard to get patients, and it’s hard to keep them."
Yes, this was part of the Chinese reforms of 2016 that I mentioned in the next comment. I don't get why people just downvote things without learning more about them.
Like China = always evil? No, they are an authoritarian system, but that does not mean that every single idea coming from them is bad or evil.
inglor_cz 1 days ago [-]
Not self-approval, but maybe look at the clinical trial reforms in China (2016). There seems to be a lesson there to learn from. They made the trial system a lot more flexible, and China has recently overtaken the US in the # of new drugs patented, about a third worldwide.
What's going on with this new drug is a somewhat novel mechanism: instead of gumming up the enzymatic action of the protein, it acts as a glue between KRAS and a common "helper" protein, that then mucks up the RAS signalling. This sort of molecular glue mechanism has had a few examples built up over the past decade, but this is a really knock-it-out-of-the-park drug. Really amazing, and because of it lots of people are focusing lots of effort on how to discover more molecular glues.
I'm glad to see a drug like this developed for people suffering from pancreatic cancer. I don't wish what my sister went through on anyone.
Damn if I don't wish it had come a little sooner.
It is a horrible disease, not least of which because it’s difficult to diagnose. By the time they get a clear bead on it, in many cases, it’s stage four and already ravaging your system.
I’m very sorry for you and your family’s loss. And I hope this drug makes it so a lot fewer people have to go through this in the future.
It’s hard as in 2013, the treatment was “get your affairs in order”. In 2023 her chances were 60/40 due to immunotherapy. Unfortunately she ended up on the wrong side of those odds. Today, the Moderna trials are improving those outcomes significantly, and I think that cancer will be fully treatable in a decade or so.
It’s almost a miracle… but the road to “better” is built on the shoulders of those who came before. I find it both a source of hope and of regret for what could have been.
> but the road to “better” is built on the shoulders of those who came before
This really resonates with me. I appreciate you sharing it. I'll be sharing it with my family, too.
Previous discussion following the data presentation at ASCO: https://news.ycombinator.com/item?id=48517199
[0] https://www.fda.gov/industry/commissioners-national-priority...
Also, the risk profile is sort of the inverse of a covid vaccine where everyone was supposed to take it.
As you can see from the control arm showing 6.7mo of survival on standard of care chemotherapy, these patients have a very poor prognosis. Is this a cure? No. Does it buy time to see your child graduate, get married, or give birth? Quite possibly.
If you ever have the opportunity to work behind the scenes within the pharma industry and/or FDA, you'd be astonished that anything ever gets approved with all the red tape and complexity along the way. Medicine is not software - it operates within the black box of human biology which is incredibly nuanced from patient to patient.
Like many who have shared personal stories in this thread, I've lost friends to PDAC. It is a terrible disease often driven by a mutated oncogene (KRAS). Many cancers have KRAS-driven subtypes (lung, colorectal, low-grade serous ovarian, etc). The clinical platform and pipeline at RevMed has potential to address many other cancers. They have next-gen RAS agents that could be even more impactful.
For those curious, RevMed posted a solid summary of the approval on their IR site [2]
[0] https://clinicaltrials.gov/study/NCT05379985?tab=researcher [1] https://clinicaltrials.gov/study/NCT06625320?tab=researcher [2]https://ir.revmed.com/static-files/0f7e4612-ad39-4c87-b266-8...
Older people have more going on, and more reasons to live, than whatever the next generations are up to. Even if we have children.
I had curative (hopefully, presumably) kidney cancer surgery 11 years ago. So far I've enjoyed travelling, socializing, working, coding, chess and other hobbies in the extra time I've been granted and I hope for decades more time to enjoy life. I don't have children. never aspired to it.
Sorry for the rant!
I also travel, socialize, work, code, play video games, solve puzzles, etc. Love all that shit.
I'd be sad to "miss" some novels, or to never see the Ocarina remake, etc. Or just the time I spend piddling around with things.
But I think if I was about to die and an advance bought me a few months of moderate quality life, it'd mostly be about seeing my kids cross milestones. I don't imagine I'd spend nearly as much time cranking through those things.
I feel similarly whenever I hear about someone expressing empathy with someone, but apparently only after realizing they are someone's daughter/brother/sister/mother whatever type of relative. What's that about? I feel empathy for any innocent victim, they're human, they're living a life, maybe a very enjoyable life even if they don't have a single relative.
You can imagine how hard it was to be sick in the early days of COVID, much less have to go to the hospital on a regular basis to receive chemotherapy for hours on end. Our family was lucky that he responded well to treatment at least and we had a few extra years with him before he passed away in late 2023.
Cancer is a terrible thing but pancreatic cancer is especially horrible due to the difficulty in detection when you're in otherwise good health. The fact that intense medical research into retrovirals has yielded something so significant as the RAS-inhibitor is nothing short of miraculous.
We were incredibly lucky to even have that time with her. Pancreatic is one of the worst cancers someone can get — both for survival and quality of life.
I’m very happy to see that we’re finally making meaningful progress on treatment.
Similar story with a guy I worked with. He went home sick one day. A few days later our boss told us he was sick and had pancreatic cancer. He came into the office to say goodbye to us a few weeks later and then died about 10 days after that.
Fuck cancer
First sign in May, followed by several doctor visits which treat the symptoms.
In late July, he heads to the ER. Multiple tests later, he and his wife get the diagnosis.
He dies less than three months later.
see https://www.wired.com/story/the-day-i-found-out-my-life-was-...
see https://en.wikipedia.org/wiki/Randy_Pausch#Cancer_and_death
CMU posted an HD version of his Last Lecture - https://www.youtube.com/watch?v=ayPMfopCe1g
A goal of research is improving early detection of these cancers but it's an uphill battle. It's difficult to increase providers' "index of suspicion" of seemingly "minor" complaints.
Childhood leukemia used to be overwhelmingly fatal, and early chemotherapy trials also only managed a couple months of remission. Researchers were even criticized for subjecting patients to harsh side effects to no apparent benefit. But thanks to that research, most patients are now cured; per capita death rates from childhood leukemia are down 14x from the 1950s, mostly driven by improved treatment.
Daraxonrasib is an incredible invention on a technical level, and a meaningful step forwards in the treatment of many cancers. We'll need a couple more equally incredible inventions to be able to cure pancreatic cancer.
> First, the personalized mRNA vaccine autogene cevumeran, developed by BioNTech and Genentech, just reported 6-year follow-up results from their Phase 1 clinical trial. 16 patients were treated, 8 were responders (showed signs of immune reaction to vaccine), 8 were non-responders.
> 7/8 responders (87.5%) survived 6 years after surgery, 2/8 nonresponders survived (25%).
> AACR meeting notes https://www.aacr.org/blog/2026/04/20/live-updates-from-the-a...
> The most important result in this small trial is that vaccine response is strongly correlated with better outcomes. But for context, the trial was restricted to patients with operable pancreatic cancer. Patients diagnosed with stage 1 or 2 pancreatic cancer have a 5-year survival rate of 12%. Patients who get their pancreatic cancer surgically removed have a 5-year post-surgery survival rate of 20%. This makes the overall 6-year post-surgery survival rate of 56% among the 16 trial patients pretty impressive. Keep in mind that the trial patients may have been healthier than average for other reasons, and small n is small n, so we shouldn't be too hasty until we see Phase 2 and 3 data.
> Source on survival rates https://www.pancreaticcancer.org.uk/information/just-diagnos...
Still early, unfortunately, so it will be a while before we see more updates.
CT scans emit ionizing radiation.
MRI contrast can buildup and be retained in the body over repeated administrations.
The scans can produce false positives, surface benign abnormalities which result in a wild goose chase, cause severe patient anxiety and healthcare burden, and result in over-treatment.
And of course doing this on a whole population level is not cost or time effective.
It will never be cost or time effective if we never try. I'm paying out of pocket every year for an MRI scan, this was my second year this past year.
The HPV vaccine will almost entirely wipe out cervical cancer: not by curing it, but preventing it entirely. Not sure if that meets your “miracle” standard, but it’s a totally unreasonable standard to apply to scientific research. By definition, a miracle is something that is not physically possible.
Research seems expensive, yes. You have to work in every possible direction, fumbling in the dark metaphorically, because you don’t know the answers yet. It’s a lot messier than giving a hungry person a meal. But hundreds of years of research have made that meal way more abundant and less expensive…
In the grand scope of the country, we spend quite small amounts on research. The U.S. GDP generates half a billion dollars in less than 10 minutes, for example. It’s less than what we spend on takeout coffee.
Ignoring the pain aspect of the disease, three months seems not to be a bad time to come to grips, say your goodbyes, tie up loose ends but not prolong suffering indefinitely and waste away.
Also, hail to healthcare systems that facilitate legal euthanasia.
I am aggressive and investigate aggressively to detect pancreatic cancer early. One even had a Whipple procedure (pancreaticoduodenectomy ), since I detected it so early.
Despite that, the longest anyone I diagnosed has lived has only been 8 months.
Sad, they were all nice people.
Killed my dad the same year he retired. Really stuck with me about how important living for today is.
No it's not a cure, but this drug is the difference between someone's mother or father making it to one more Christmas, or Birthday, or other life milestone.
Father in law started chemo a few weeks ago and his condition deteriorated quickly, he's been at the hospital since; switching between ICU and general care. His abdomen fills up with fluid, around 6 liters every 5 days, draining the fluid plunges his blood pressure and he end up in ICU. They supply Albumin until blood pressure stabilizes and send him back to general. Only after the first chemo session the oncologists have stopped the treatment saying he's no longer eligible for chemo because of his over all health.
We're lucky enough to live an hour away from Johns Hopkins (though that's not the hospital he's currently at) and had an appointment scheduled but had to cancel since he's unable to walk.
The oncologist mentioned that daraxonrasib was available as an option when he first started chemo, but said he would only be eligible for it after trying chemo, so we know the drug is available.
Are there any tips from HN on how we can approach getting this medicine for my father in law?
I would suggest you have your physician submit a Expanded access request immediately, because the same page says that they will close this program after FDA approval as they transition to commercial use, but the timeline for that is unclear.
I hope many others are helped by daraxonrasib, the key factor seems to be how early the cancer is detected, because it is an extremely fast acting disease.
Steve Jobs had pancreatic neuroendocrine tumor, which is a rare form of pancreatic cancer.
Same organ, but fundamentally different diseases.
Pancreatic neuroendocrine tumor is usually quite treatable, but Steve Jobs delayed surgery for almost a year to try to beat his cancer "naturally" - with a fruit diet, herbs, and acupuncture. Were he had gotten the surgery right away, there's a very good chance the cancer wouldn't have spread and he would be alive today.
Beyond that, from tfa
>Rasonque improved median overall survival to 13.2 months compared to 6.7 months for standard chemotherapy.
Fuck cancer.
Remember in COVID when results. Came in and they took a month to schedule the meeting?
Jake Seliger, HNer, jseliger - https://news.ycombinator.com/user?id=jseliger, who died a couple of years ago, had exhausted the current standards of treatment for head-neck cancer. Drugs available through clinical trials were his last option.
But the workflow to access drugs via clinical trial is terrible. Directions/Instructions aren't documented. Unwritten limitations and optimizations.
Jake and his wife documented his path through the process.
see https://jakeseliger.com/2023/07/22/i-am-dying-of-squamous-ce...
also see https://jakeseliger.com/tag/clinical-trials/ and https://bessstillman.substack.com/t/clinical-trial
Also read https://bessstillman.substack.com/p/the-seliger-act-testimon... for a literal post-mortem view of the clinical drug trial process.
"The biggest bottleneck in the clinical trial system is recruitment and retention. It’s hard to get patients, and it’s hard to keep them."
Yes, this was part of the Chinese reforms of 2016 that I mentioned in the next comment. I don't get why people just downvote things without learning more about them.
Like China = always evil? No, they are an authoritarian system, but that does not mean that every single idea coming from them is bad or evil.
That number was ~ zero mere ten years ago.