CRISPR tech selectively shreds cancer cells, including "undruggable" cancers
innovativegenomics.orgOver the past 1-2 decades there has been unbelievable progress at the basic technology level but most people are unimpressed because they haven't translated yet due to not individually being sufficient to cause an explosion of progress. IMO, we're starting to see it finally as so many different technologies have gotten so cheap, fast, and good.
[0] The covid vaccines collectively were faster only due to the fact that when money is no object you can parallelise a lot of options and can pipeline the testing stages rather than waiting for full review and another funding round before progressing to the next stage
[1] Where they-don't-tile-but-we-did-it-anyway animated gif backgrounds are the metaphor for home kits to make random things bioluminescent: https://www.the-odin.com/gfp-bacteria/
10-20 years for an Alastair Reynolds' style Indoctrinal Virus? I hope not, but I can totally see it happening eventually.
If spending billions was the main trick, we’d know it already.
As a result, life science researchers are more price-taking than proce-setting when it comes to their wages / salary. If money is the motivator, then the market as-is isn’t addressing this one.
There's a wide world outside big tech, Silicon Valley, and software in general. It only tends to be a bit less visible online.
Private pharmaceutical R&D spending in the U.S. is around $100bn per year [1]. NIH spends another $50bn a year on biomedical research [2].
That eclipses total investments into adtech per se, which generously counted shouldn’t exceed $50 to 60bn. (And that only by counting like a third to a half of Google, Amazon, et cetera R&D and capital spending as adtech.) More precisely counted, it probably doesn’t exceed $10bn.
[1] https://phrma.org/blog/phrma-member-companies-rd-investments...
[2] https://www.science.org/content/article/final-nih-budget-202...
Factors that would make it more attractive our lower interest rates, higher returns, or faster development.
All of these are theoretically possible to adjust, but the last is most feasible to do in a tailor-made way through FDA review and approval reform. An ambitious example would be allowing conditional Market approval after Phase 2 and treating phase 3 deliverables as post-market commitments.
Advancing the revenue curve two to three years while maintaining the same patent expiration dates can dramatically change the ROI of a pharmaceutical development program.
Beyond this, even conditional Market allowance allows firms to better gauge Market interest and validate Financial investment models sooner.
Similarly, there's also some really low hanging fruit in this area to help manufacturers get to Market faster. For example, the FDA approval of trade names and label content is one of the last steps in Market authorization. Moving this earlier in the process would help products itself sooner and start producing Revenue sooner. Imagine having your billion dollar annual revenue shift out a quarter because the FDA wanted some last minute change to how a cartoon belly button looks in the instructions for use.
Adtech works because there is a lot of money in it. There is a lot of money in it because people seek quick entertainment, and we have a LOT of people driving the demand.
Now compare that to cancer research. There's no short term gratification about it.
And even more brilliant minds are defeating it, every day. I have doubts about how useful they would be in a research lab.
Also wonder, outside of politics and economics, whether there's a social and cultural component that can contribute. TV shows, movies, books, and other forms of media that put science and scientists in the spotlight in a positive light can be tremendously inspirational.
Then the money will flow.
Cancer prevention is downstream from that, as cancer frequency grows exponentially with age. If you can truly rejuvenate a person, you will also reduce their risk of cancer.
> Much like other CRISPR therapies, delivery is a critical challenge, i.e., getting the large genome-cutting enzyme to all the targeted cells efficiently.
makes me think this is in vitro so far. So, years to decades away from being available for actual treatment in humans. Still good news.
Like many things of this nature, people keep bringing it up because it sounds Very Scary and Very Dystopian - not because it's worth giving an actual fuck about.
If that's not what you want, you'd need something like a virus to spread it. But then you have to ask yourself: what if that virus mutates? The specialization to certain gene markers is an evolutionary disadvantage, so evolution will tend to make it lose that restriction. Ooops.
Suppressed debate is almost universally due to biased/captured moderation teams aggressively using bans.
People shouldn't be blocked from commenting because their karma goes negative. Spamming, hateful talk, etc should be a completely different system. Just because what you say is unpopular (in one place mind you) doesn't mean your words should be hidden.
CRISPR was the cause of a huge patent case and likely led to a change in US patent law because of the impracticability of deciding who did something first in the laboratory.
It continues to influence research as some nations took a while to decide how they would resolve their own researchers' CRISPR claims with respect to MIT/UC Berkeley.
And yet... all the research has continued apace.
Edit: the CRISPR patent cases are continuing even today
https://news.berkeley.edu/2025/05/12/federal-appeals-court-s...
https://www.broadinstitute.org/crispr/journalists-statement-...
Chemo, radiation, and CRISPR will kill everything it can reach that is susceptible. That leaves everything that was unreachable or resistant behind to start growing again.
Kill cancer cells is easy. Killing ONLY cancer cells is very hard.
Counting all viral vector therapies that have been approved, we’re sitting at 19 approved therapies versus 1 for CRISPR.
I think CRISPR ideas in a lab are just an easy way into the mainstream press, but viral vector delivery is the real future. It just didn’t get the same news cycle, for whatever reason.
I usually end Legend after the mannequin trap, and end Sunshine after the transit of mercury.
The paper describes Cas12a2. This is a different mechanism with discovery origins in - of all things - agriculture. It does not attempt in any way to reprogram cells. It uses a guide protein to locate a specific mutation with exacting precision and, when it activates, unleashes total destruction of the cell.
The implications of Cas12a2 on undruggable conditions that exhibit known driver mutation profiles is profound.
Source: I have personally funded novel research based on Cas12a2 for an undruggable condition I have. I have personally seen my condition "cured" in vitro using this technology and it left all of my WT cells unharmed. Some of the researchers I've funded are co-authors in the paper linked. I am a layperson in this field (I'm a SWE, not in biotech), but I am happy to answer questions.
The approach I'm reviewing now uses lipid nanoparticles (LNPs) for delivery. It isn't great for targeting my bone marrow condition but its workable. The team hasn't optimized it at all, either. There are also viral delivery mechanisms that I haven't studied yet.
The collateral damage problem is the backpressure on the delivery problem. If you get really good at delivery, you can destroy A LOT of cells very quickly. The human body (usually) responds to these events by releasing a lot of pro-inflammatory cytokines. This can lead to cytokine storms or worse.
As you "get good" at killing the target cells, the net effect can turn bad. It will probably be a balancing act.
Yes, this is an approach. This starts to exceed my understanding of the problems the teams are facing - but there are concerns about the efficacy of Cas12a2-based approaches fading. Not because the cells adapt, but because your immune system starts acting funny in the presence of the payload.
I don't recall the specifics but there seems to be a window of opportunity for these things.
> If you get really good at delivery, you can destroy A LOT of cells very quickly.
You can destroy cells quickly. Ok. So the question is: how do you detect specifically only cancer cells via lipid nanoparticles? That was already a problem years ago with Herceptin. The rationale that is always used is that "we need to do something" for certain aggressive cancers. It has never been a super-effective technique, despite all the promo of how monoclonal antibodies are so accurate.
> As you "get good" at killing the target cells, the net effect can turn bad. It will probably be a balancing act.
That's already the status quo in the whole cancer field. I don't think that more than sloppy accuracy is acceptable for any gene therapy - and the off-target cleaving of CRISPR has always been the number #1 problem here.
You don't. Healthy cells will also get these nanoparticles, but without the triggering DNA sequence, the mRNA payload will remain inert and eventually will be degraded.
This is my understanding as well.
Valid critiques of Cas12a2 must acknowledge the mechanistic differences between Cas9 and Cas12a2. There is no research to suggest Cas12a2 is "sloppy" and significant research that demonstrates it is not "sloppy."
I appreciate the skepticism but I would encourage you to study the actual mechanism discussed in the paper.
> other folks dealing with a tough diagnosis
The toughest part has been the spiritual journey. Loneliness unlike anything I've experienced. I felt forgotten without the opportunity to be known in the first place. I was happy - and emotional - to learn I wasn't alone. It took me 2 years, but I've found my people.
I've come to terms with what's happening to my body and that I may not benefit from my efforts.
Background: ~3 years ago I was diagnosed with a very rare MPLW515L-driven blood cancer known as a myeloproliferative neoplasm. My hematopoietic stem cells (HSCs) acquired this mutation and they produce busted downstream products.
Most notably, one of those downstream products are hyper-lobulated megakaryocytes that spew inflammatory cytokines into my bone marrow and destroy the bone marrow niche over time. The destruction happens specifically because the inflammation mobilizes stromal cells and they erroneously produce scar tissue (fibrosis) all along the walls of the good, spongy marrow. There are other sources of damage but this is the one path most aligned to abbreviated survival and transformation into AML.
In effect, my bone marrow is rusting and very slowly failing. The failure could speed up with the acquisition of additional mutations or any other systemic inflammatory condition.
Anyway, 3 years ago my first retail hematologist told me "it's rare, you're fine, take aspirin and go home."
I couldn't accept that - this seemed bad. I decided that if I wanted to know the truth I needed to physically stand in front of the foremost expert in the world on the topic and ask them "what is the state-of-the-art?"
I came to this conclusion after about a year of reading all the most well-cited academic papers about AML, Myelofibrosis, and Essential Thrombocythemia. In particular, anything that mentioned MPL. There are virtually no papers mentioning MPL.
To put that in perspective: 500,000 patients in the US deal with the broad disease category. 5% of those are MPL, and 40% of those are the -K variant. So 10,000 people - which means anything targeting it would be well into orphan drug designation territory. I'd need to find a pretty niche researcher.
So, I laddered up the academic food chain using a little cash (donations), emails, airline tickets, and conference admission. ~2 years after my diagnosis I found myself in a closed-door session called the MPN Roundtable in Chicago with 100 of the foremost experts in the world. No cameras, no transcripts, just some of the greatest minds in the field earnestly debating the path forward to a cure.
I listen carefully to them, ask dumb questions, connect dots across research. I rehomed my care to an academic research hospital specializing in MPN research, and started funding research on the condition it includes my specific MPL mutation. Researchers happily oblige.
Cas12a2 was the keynote topic at this year's meeting and there was _very little_ dissent.
Hopefully you get great progress on your research but I just wanted to reassure you that the name sounds scary but the current treatment appears to work well and hopefully gives you enough runway to find your cure.
Even a charitable read is condescending. This person just wrote they are in the innermost research circles. I think they are beyond the "scary name" - needs reassurance phase.
As an aside if you end up cryogenically freezing yourself for a future treatment don't forget to actually cure your boneitis when they thaw you out.
How much overall has this costed you? Do you think that a middle-class person could afford to do what you did?
> So, I laddered up the academic food chain using a little cash (donations), emails, airline tickets, and conference admission. ~2 years after my diagnosis I found myself in a closed-door session called the MPN Roundtable in Chicago with 100 of the foremost experts in the world. No cameras, no transcripts, just some of the greatest minds in the field earnestly debating the path forward to a cure.
Why don't they allow recordings at the MPN Roundtable? It could be useful for others to learn from.
For this project, seed capital low six figures. I am collaborating with family and friends, non-profits, and using doubling mechanisms available to me to at work to fund the very early speculative bench research. This is where we are and its sustainable today.
Once we have the basic tech worth scaling up - to raise the first round of capital, I estimate $1-2m with a wider friends & family and angel investor round. This will be early de-risking research and delivery mechanism testing.
Beyond that I can see a path to a ~$20m round to further de-risk any assets that come out of these speculative efforts, but I haven't gotten this far.
In rare disease therapeutics the challenge isn't raw capital, it's finding the _right_ capital that understands how assets like these get de-risked and can tolerate the shape of the upside. Anything CRISPR-based is usually not a chronic therapeutic, so that disqualifies most of big pharma. Acute, curative technology like this requires informed capital.
> Do you think that a middle-class person could afford to do what you did?
Yes.
In the rare disease field even a small amount of capital attracts enough attention to have meaningful conversation with bench researchers. If you're willing to travel to the niche conferences, ask dumb questions, grind out the studying, and approach the speakers after their sessions.
Researchers respect people who do their homework and mobilize to meet them. They want (need) to hear from patients and caregivers - so they tend to listen very carefully.
Fun fact: I've had multiple researchers ask me for samples of my bone marrow. Has only happened in-person :)
> Why don't they allow recordings at the MPN Roundtable? It could be useful for others to learn from.
I don't know, it's been going on for a while. I can speculate: they're discussing pre-publication data, some of which had come out of their labs only hours prior to their presentation. It's completely unfiltered. I think there's real risk of some of the things that are shown being sensationalized or taken out of context.
The audience is trained and practiced in keeping a sober, skeptical lens on everything they see - so it's more about the debate and tear-down of the early data for the betterment of the niche.
There's zero attempt to hide anything, it's just a forum for collegial debate.
Yes! That's the next step. There wasn't a mouse model for my variant so they're building that, too. But in vivo testing should be underway this calendar year.
If it were to work, gene therapy as-is would be possible. Which it is not, not even for those overpriced therapies. I have no doubt that sooner or later it will happen, as the problem space is finite, not infinite, but I simply don't see the correlation here.
> The implications of Cas12a2 on undruggable conditions that exhibit known driver mutation profiles is profound.
So what does this change exactly? Humans defined it as "undruggable conditions". You can reason this is an improvement, but I still see it in failure-territory. If it were to work, gene therapy would be an accurate - and affordable - technique. Which it is not right now.
> I am a layperson in this field (I'm a SWE, not in biotech), but I am happy to answer questions.
How does "answering questions" offset the technology being inferior right now?
Others in this thread may be able to give a better analogy, but I'll try:
Cas9 is like open heart surgery on millions of cells all at once. We know the specific outcome we want - a surgical replacement of a sliver of a sequence - but just like open heart surgery, it's an inexact operation. Cas9 tolerates mismatches which categorically allows off-target matching. It also operates on DNA, so any off-target effects reprogram the cell's primary source code.
We want the Cas9 "patient" cell to survive.
In contrast, Cas12a2 is key-locked self-destruction switch. It targets single-stranded RNA transcripts with a specific guide protein. So the specificity is two-fold: the guide protein doesn't tolerate mismatches, and its operating on a _downstream byproduct_ of the DNA. When the key (guide protein) matches, it unleashes total destruction within the cell.
We want the Cas12a2 "patient" cell to die.
> If it were to work, gene therapy would be an accurate - and affordable - technique. Which it is not right now.
Correct on the first point. If it were to work, gene therapy could be more common. I do not know how to make it affordable, yet. In the models I've built to commercialize this I estimate a Cas12a2 treatment would cost approximately as much as a bone marrow transplant.
> How does "answering questions" offset the technology being inferior right now?
In fairness, asking and seeking answers to questions is all I have right now. There is no cure to my disease so the upside - no matter how futile you may perceive it to be - to me, is infinite.
If I can solve it I may get a few more years with my daughter. If I can't, I can show her how to live fighting for an answer that may never come.
You're not wrong, you and I just have different perspectives on the upside.
It’s only a matter of time before the next better thing shows up.
The public in general doesn't have a good understanding of basic genetics and I blame high school science curriculums for not covering it well enough. Too much time is wasted on Mendelian genetics without covering the Central Dogma.
You basically cannot "edit" your somatic DNA in a meaningful wholesale way since every single cell in your body has a copy of the DNA, and it's a foolish endeavor. What you can conceivably edit to good effect is your germline DNA, stem cell DNA, or modify mRNA expression (e.g. retinoids; yes putting retinol/adapalene cream on your face is "gene therapy"), or introduce foreign mRNA for your translation machinery to co-opt (e.g. mRNA vaccines).
Expressing mRNA that doesn't exist in the genome, that would be gene therapy. Or just a virus.
The CRISPR-Cas9 gene-editing tool was developed in 2012, so I don't find it surprising that merely 14 years later, there's only one approved treatment. From discovery to approval, drug development often takes 10-15 years, and often much longer for novel techniques. So I'd say it too early to call it overhyped for treatments.
Finally, I think we'll see a lot of treatments that don't use CRISPR-Cas9, but related gene editing techniques, but it'll take another 10 to 20 years.
Take a look at https://en.wikipedia.org/wiki/MRNA_vaccine#History for how long another novel technique has been in development before it became really widespread with the mrna-based covid-19 vaccines.
mRNA vaccines are also quite different. Do they modify the DNA? Of course not. So that's already very different.
> mRNA vaccines are also quite different. Do they modify the DNA? Of course not. So that's already very different.
And yet it took more than 30 years after the first mRNA experiments to develop a successful vaccine. Why it should be so much faster for CRISPR & Co?
As far as I know a few labs in this space are operating under the basic question, "why haven't viruses killed everything by now?"
So this category of research is more or less the answer.
> Do mammals have a CRISPR analog?
Not exactly. There are things like https://en.wikipedia.org/wiki/Ribonuclease_L that nuke cells and are stimulated by interferons. This might be why interferon injections are common chronic therapeutics for diseases in this space.
The closest thing we have is probably whatever adaptability B or T cells can muster on their own? I'm sure someone lurking in the comments has a better answer.
The comparison is kind of a category error. One is a DNA editing technique and the others are deliver platforms. I recall the hype mostly being how revolutionary it could be, not comparing it on a timeline to specific technologies that are at different levels of the stack.
Tens of thousands of papers have made important scientific advances using it successfully and CRISPR-Cas methods are used routinely throughout almost all of biology.
This is like calling PCR "overhyped" because PCR-based infectious disease diagnostics are limited.
As with any cancer treatment, it's likely the tumor will evolve resistance. My guess is that cells will find ways to reject the lipid nanoparticles used to deliver the CRISPR/Cas mRNA and associated guide sequence(s), either via modifications to the cell surface (preventing LNP uptake) or via changes to endosomal/lysosomal pathways (causing the mRNA payload to get degraded before it has a chance to be translated into protein).
[0] https://pubmed.ncbi.nlm.nih.gov/28575452/
That's how we deal with HIV. No single HIV therapy (so far) is effective enough to suppress the virus all by itself, but a combination of them provides a barrier that is too high for mutations to jump.
The new therapies will also likely be applied after surgical resection and/or classic therapies to reduce the bulk of the cancer.
Once we solve the cancers we know about, they're solved forever, with the one caveat that more people will live longer, so that will increase the window for eventually still ending up dying to one of the cancers that happens to have a non-evolved built in resistance to this or that treatment. Which is a great deal of course, especially if it's a treatment that sounds way less destructive of QoL than chemo, radiation, etc.
No, but there is "be a better/stronger cancer cell and don't succumb to whatever therapy is killing its neighboring cells." It's exactly akin to how dosing isolated populations of bacteria with antibiotics selects for individual cells that are resistant, which then multiply and dominate [0], just like a tumor.
(barring the transmissible cancers article that your sibling comment linked to, but that's not the common case)
The rare exception: https://en.wikipedia.org/wiki/Clonally_transmissible_cancer
Another curious case of "cancer being an organism" is the HeLa line derived from cervical cancer cells taken from a woman called Henrietta Lacks.
I've heard about drug resistance in bacteria leading to slower growth / reduced virulence. Maybe the same would occur with cancers. A drug that could effectively switch an aggressive cancer into a slow-growing one wouldn't be the worst thing.
Yes, if the LNP could be engineered to target an essential surface receptor, which is still a very tough problem. It would also not solve the issue of the payload successfully entering the cell but being subsequently degraded.
>I've heard about drug resistance in bacteria leading to slower growth / reduced virulence. Maybe the same would occur with cancers. A drug that could effectively switch an aggressive cancer into a slow-growing one wouldn't be the worst thing.
This is essentially how treatment for chronic lymphocytic leukemia happens (hence why it's called "chronic"). People with CLL can stay on BTK inhibitors for decades, often until they die of other natural causes.
Another question: how does this approach compare to trying to repair the pathogenic variants in the cancer? I asked here about that approach recently and the response was mainly about delivery difficulties: https://news.ycombinator.com/item?id=48285386
As is often the case, it's a lot easier to indiscriminately destroy than precisely (re)build.
this is the concept of genetic baggage, and metabolic budget.
there is only so much energy to a cell, and scant amounts to "waste" on preservation of something that is not used. in the long term, carrying unused properties are disadvantageous, and reduce reproductive output [replication]
the result is "unfettered" oncocytes outgrow those with baggage, and occlude access to resource. if there is no challange that reduces population of nonresistant cells, the resistance will be minimized and extinct in the face of large disparity of success.
If p53 is reactivated, the cancer cell dies.
https://en.wikipedia.org/wiki/P53
Perhaps a different mutation that disables p53 could evade the pattern match.
This article is all about p53.
Edit: This section of the wiki best explains this critical cellular component...
p53 regulates cell cycle progression, apoptosis, and genomic stability through multiple mechanisms:
-Activates DNA repair proteins in response to DNA damage, suggesting a potential role in aging.
-Arrests the cell cycle at the G1/S checkpoint upon DNA damage, allowing time for repair before progression.
-Initiates apoptosis if the damage is beyond repair.
-Essential for the senescence response triggered by short telomeres.
evolution isnt about generating a response to a challenge, its about differential success.
those cells [oncocytes] that have properties conferring resistance carry it as un-utilized baggage, those without said properties make a living without that fetter.
the selective factor comes into play when payloaded LNP [in this case] facillitates destruction of "nonresistant" oncocytes and spare the "resistant"
the resistance is not generated in response to the challenge, it is already present, and confers survivorship in the face of the administration of the drug.
The post on AI and and cures for cancer is https://www.writingruxandrabio.com/p/a-response-to-dario-amo... .
Same here. Are you and your care recipient familiar with the Optune Pax device that the FDA approved in February?
https://www.fda.gov/news-events/press-announcements/fda-appr...
My father's been using it since April. It's a little cumbersome and only improves overall survival rates by about two months over chemo alone, but we're hoping that it helps him remain relatively healthy until Daraxonrasib becomes available.
We should be alright. We're on track for the expanded access program. Also, it's a long story, but she was taken off an Irinotecan-containing regimen prematurely about a year ago. In hindsight, she was clearly reaponding very well to that particular drug, so we've got that in our toolkit.
My partner of many years had one of the nastiest cancers around, one with no targeted treatments. She went through an experimental combination of existing drugs. Some of the side effects included:
* Her heart stopping during a drug infusion. This happened multiple times over the 18 months of treatment.
* Disseminated fungal infections.
* Sepis because holes were developing in her GI tract.
This was a good response. Other patients just died from the drug combination.
This is what going slowly looks like in the world of cancer treatment.
This makes some sense in terms of compassion and matching new experimental techniques with patients with no hope, but it skews the results highly negative because the patients are already very close to death's door. It does not provide an accurate signal for what the results would be if we gave them to less sick people.
I don't think any of this can be changed without large-scale social acceptance of greater risk in clinical trials and significant support from the government.
It provides an excellent signal because we want to prove that these drugs are doing something that the standard of care is unable to.
There's this sense that medicine is easy and some evil cabal are limiting health to their cronies. Most medications never get to trial for their intended indications, and most fail trials. There's no reason to believe oncology medications are somehow uniquely unlikely to go through this well-described process of failure.
We relax ‘do no harm’ quite a bit when the alternative is certain death. People like to try stuff in order to hang on to hope. Towards the end I became convinced that she made the wrong choice to do aggressive interventions. Quality of life was very bad.
On the other hand, she gave it her all trying to survive. Hopefully that was satisfying for her.
Because of this initial trials consume lots of medical staff to deal with the potential side effects. Normal side effects for cancer treatments include:
* Your gut lining dissolves, your shit leaks into your body cavity, and you get sepsis.
* Your heart stops during the infusion.
* Cumulative poisoning that nobody understands. (E.g. some agents have lifetime limits, and if you go beyond that, then you die. Guess how we found out.)
* Your immune system, and you get things like disseminated fungal infections.
This puts a limit on how many patients you can put into a trial. I'm under the impression that cancer trials are pretty much always full.
What's more crazy is that we're slowly going from millenia, to decades, to likely years in the near future from being presented a biological problem and achieving the next milestone in solving it. We might have "AI", but we also have brilliant minds right now that are speeding up development to a pace that would be unimaginable just few years ago.
The big success story, about 20 years old now, is testicular cancer. You can have metastatic testicular cancer with tumors all over your body (like Lance Armstrong had) and they can cure it. They use platinum based chemotherapy and it's not really well understood why it works for testicular cancer, but not others.
The story with childhood leukemias is similar. They figured out how to combine a bunch of chemotherapy to get the cure rate up pretty high. Leukemia in a child used to be (1990s) 90% fatal, it's like 10% now.
Besides those, most of the advances in the past few decades come from early detection/ surgery or just prevention (stop smoking).
There is some hope though. When people first started studying cancers at the molecular level, one of the first things they noticed was how often a gene called Ras was mutated in different cancers. It turns out that designing a drug for Ras was really hard, but it finally got done, it's called daraxonrasib. They just released phase III human trials with this drug in pancreatic cancer a week or two ago and it destroyed the standard of care (Chemotherapy), but that is saying people who were dying in 1-2 months were still alive after 5-6 months.
The former senator Ben Sasse was diagnosed with metastatic pancreatic cancer last December. Historically, that's like 5% survival rate for 5 years. He is on daraxonrasib. We will see how it works out.
Page 2 has the figure. Getting people to not smoke has been the most effective treatment in our lifetime.
Public health is a really big deal, and RFK et al are a disaster for the nation.
Getting older, I'm not subscribing to that, but it sometimes feels like the RFKjr -style interventions are calculated. Then again, this theory makes zero sense when dismantling herd status for measles (I don't think 'natural measles survivors' are genetically 'better' than the rest of us)
But on a lighter note: is there any belief more certain to spoil?? My god. Don’t underestimate the moral worth of futureYou, folks. I guess delighting in their assured regret is a bit of a guilty pleasure, but it helps!
RE:RFK, I think you’re indeed overestimating their intentionality. They intuitively feel that measles wouldn’t affect them because they’re stronger, and would do their best to dance around that belief if pressed beyond their comfort zone of cherry-picked facts.
But really, they’d much prefer to just not think about that part altogether IMO; ‘MAHA’ is much more about hypernaturalism & tradwives than it is about public health. This is all just annoying scaffolding to them.
Though I don't subscribe to utilitarianism or the notion that the value of an human being can be reduced to its economical aspects. It's not my moral compass.
https://www.abc.net.au/news/2026-06-08/professor-richard-sco...
Anyways, I studied SCLC in grad school and saw lots of scans of people with tumors from their heads to their feet, and saw the enormous resources dedicated to caring for SCLC patients and to searching for a cure. It’s hard to overstate how profoundly evil the cigarette companies were and still are. They got people (children) addicted knowing what was coming for them, knowing they were killing them in horrific ways. Now we all get to pay for that in funerals and tax dollars.
https://en.wikipedia.org/wiki/Oncogene
at the simplest level, the particular gene, and particular perturberance, sets the "type" of cancer.
there will most often be additional genetic abnormalities giving nuance to the character of the oncotype.
the tumour is originated from a cell type of specific differentiation, and developmental potency, further widening the pool of possible cancer type.
immunotype of cancer also sets the relationship between cancer and the body.
the cells of the body are setup for a functional death and replacement so when you try to rescue a particular cell [or cohort] you are fighting against how the grand scheme of tissue maintenance operates.
unless you have concern for a particular long lived cell, it is best to destroy the tumour cell, and let the next cells in line replace them.
it is still a multifacet strategy being developed, inhibit the genetic properties of the tumour, and target the immunotype for destruction.
Just as attacking such problems with rocket launches involves hundreds of different approaches, that’s the situation for cancer. I’d also point out that this is why it was really not trivial to identify microbial and viral causes of disease in the 19th century - especially since we now know that certain kinds of infectious disease can themselves result in cancer initiation. It’s definitely a hard set of problems.
I would also add, there was a concerted effort by industry to promote ‘inherent genetic malfunction’ as the cause of cancer in the late 1990s and early 2000s, but the reality is that exposure to industrial carcinogens tracks closely with a wide variety of cancers (skin, digestive tract, etc.). This was a very deceptive and dishonest approach to avoiding regulation.
Basically everything that was invented up to 3 years ago was invented without the help of "AI". And that includes "AI" itself, for we, humans, invented that too.
So yup, humans can be quite resourceful.
Cancer is best understood as a family of tens of thousands of diseases. They're a whole range of different genetic changes that can happen which result in similar categories of symptoms and consequences. They can also be incredibly complex, such as being the result of hundreds of stacking genetic defects acquired over a lifetime. There can be a thousand varieties of one specific type of lung cancer, and they might all react differently. Some of our solutions might work on a lot of them, but others might only work on a handful. And we're at the beginning of figuring all this out.
CRISPR may eventually allow us to genetically profile a cancer and design highly targeted medications to cure them, but we don't know yet how well it will work. It may only work on a portion of them. It may have worse outcomes than chemotherapy or radiation. It's nice to think that we're going to find a magic solution to the entire problem, but things almost never work that way. I think we're going to be able to resolve a wide range of issues, but I don't think it will really cure cancer as a whole.
There's a site that lists the AWS instance types, so maybe...
[1](https://www.propublica.org/podcast/revlimid-cancer-drugs-fda...)
So one needs to figure out a delivery method that is efficient enough, and that doesn't elicit an immune response. But I guess one can analyze the cancer in the lab and figure out which receptors it expresses, and then bind to those? We could have a toolkit of different delivery methods, tailored for each patient's cancer.
[1]: https://www.clinicalcorrelations.org/2019/02/22/the-history-...