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’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.
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.
Previous discussion following the data presentation at ASCO: https://news.ycombinator.com/item?id=48517199
[0] https://www.fda.gov/industry/commissioners-national-priority...
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.
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.
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
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.
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.
That number was ~ zero mere ten years ago.
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...
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-...
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.
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.
"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.
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
And once you find something with a screening you can’t unfind it. The patient or at least their doctor now has that knowledge and has to live with it and actively decide what to do about it.
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.
That only underlines my point. The HPV vaccine was in not really a product of cancer research, in terms of the cancer itself. It’s purely a multivalent viral vaccine with the munificent effect of preventing several cancers and nasty genital warts as an additional motivator. It has saved many thousands of lives that would have been lost with the best available cancer treatments and avoided their costly and excruciating effects.
It’s too early to write off cervical cancer, besides HPV-negative ones, there are evolving strains not covered and a huge pool of viral reserves worldwide and among the unvaccinated in the USA. A universal mandate won’t happen and coverage isn’t high enough to eradicate it.
Prevention is important for almost all cancers. There will likely be other vaccines in the future targeting carcinogenic infections but most cancers don’t have a simple infectious cause. Cancer is a family of nasty diseases that has time and again defied all pronouncements of impending universal cures.
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.
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.