Researchers uncover on/off switch for breast cancer metastasis in mice
news.stanford.edu
news.stanford.edu
These famous researchers are actually at UCSF, not University of San Francisco. UCSF is really a leader in breast cancer the world over, far more influential than Stanford's much smaller amount of faculty on the topic. So it's a bit weird to see such a basic mistake.
> Additional co-authors are from the University of California, San Francisco, and Arc.
For all the criticism FDA gets, they should also get credit for leaning into new approaches to testing drugs like adaptive trials. Part of why the US remains one of the most innovative countries.
university of san francsico
to someone not from the area this is a very easy mistake to make
I tried to find any reporting on this, and while apparently it's happened to a few students (they applied, got accepted, then discovered the school is in rural Ohio and not Florida) but not the specific case of it happening with an athlete (seems really unlikely).
You can literally send physical mail to Indiana University of Pennsylvania, Indiana, Pennsylvania.
Washington University in St. Louis
>> Patients with high ENPP1 levels had low response to pembrolizumab and high chance of metastases. Those with low ENPP1 levels had a high response to pembrolizumab and no metastases. ENPP1 predicted both response to immunotherapy and likelihood of relapse.
Keytruda/PD-1 blocker:
https://en.wikipedia.org/wiki/Pembrolizumab
ENPP1 blockers already exist:
https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.16_suppl.e1...
I'm most interested in head and neck cancers, and pembrolizumab (Keytruda) is only effective in 20 - 30% of patients; see e.g. https://ascopubs.org/doi/full/10.1200/JCO.21.02198: "In the phase Ib KEYNOTE-012 study of pembrolizumab monotherapy in R/M HNSCC (N = 192), objective response rate (ORR) was higher in patients with PD-L1 CPS ≥ 1 than CPS < 1 (21% v 6%; one-sided P = .023)."
A lot of oncologists I've talked to also think PD-L1 expression is overrated as a marker of pembro effectiveness; obviously there's something going on, with higher PD-L1 expression being net better in terms of pembro utility overall, but the data are noisy and lots of exceptions abound. I'm also not sure how reliable PD-L1 expression tests are. My tumor was tested once by a well-known-in-the-field company called CARIS, and it showed a 20% Combined Positive Score (CPS). Another test done by the Mayo Clinic showed a 5% score. Who's right? Who knows. No one I've talked to. The attitude seems to be that no one is convinced the PD-L1 tests are highly accurate, and that once the CPS is above 1%, pembro's effectiveness is a crapshoot anyway. I got five doses of pembro and failed it, utterly.
They found a correlation between a protein (ENPP1) and breast cancer metastasis that they feel is a very strong signaler for pembrolizumab immunotherapy resistance. This would be helpful information to help get to the right dosage of medicine faster (or skip a class of drugs entirely), which might save weeks or months of taking a drug that effectively is neutralized by the resistance.
Additionally, hopefully new medicine will (after more research) go after this protein and see if attacking it allows the immune system to better resist cancer itself.
It's also worth noting that two of the researchers involved in this work own a company to try to utilize patents around this work.
Is the implication that there is bias, or are you implying there is reason to be hopeful that it makes it to market quickly?
I consider the speed of light being 299,792 km per second as worth remembering even if I have no specific use in mind.
This isn't even true. In the example you gave, you clearly remember the speed of light because you think it may be useful someday.
When someone believes a fact is important or "worth noting", they used some reasoning to arrive at that conclusion. Whether or not that reasoning is flimsy is another matter.
In this case I think there are a few reasons of note which were already alluded to, but I don't personally think it need call any questions about the validity of the experiments and the other reasons being around the potential future value of associated company, any opinions of which are for the individual and their financial advisors to consider.
I wasn't aware of the fact there was already a company created for it but it does say something about the confidence these researchers have placed in the results, even if that may not be noteworthy, per se, regarding the results.
On one level it’s essentially random trivia you can easily lookup, but on another level it’s fundamental in a way that few things are. Individual mutations from random events wildly shaped human history making most facts people remember essentially happenstance. However, c is more closely tied to the underlying aspects of reality.
Of course it is. This is one of those 'only on HN' moments. You absolutely can be cognizant that a fact may give rise to any number of competing interpretations, and you can understand those interpretations to be significant if true, while not endorsing them.
>When someone believes a fact is important or "worth noting", they used some reasoning to arrive at that conclusion
Again, you can understand that a fact gives rise to certain interpretations without endorsing those interpretations, and this could nevertheless be enough of a reason to merit sharing the fact.
My point is that when one determines that a fact is notable, there is an underlying reason for making that determination, whether it involves several "competing interpretations" or not. It is perfectly reasonable to ask for that underlying reason so I can assess the validity of the statement. If someone refuses to give it, as we've seen here, then its reasonable to dismiss their assertion. I'm not responsible for justifying their own argument for them.
As for the 'only on HN' remark, I think that was unnecessary. At any rate, this will be my last comment on the subject.
Didn't seem like it to me (personally speaking).
I felt that it was worth noting because, depending on the viewpoint of the reader, that information could be seen as a positive or a negative, and could have an impact on their viewpoint.
1. The existence of the company suggests that there might be a meaningful or profitable future from what has already been learned.. commercialization of this information might be more readily possible.
2. Someone who's cynical might question the validity of the research and/or the motives of people involved.
I certainly have my own opinion, but I also have not deeply researched this subject, or the researchers involved. I was curious to get some high level information on this topic so I read the article. I felt it was hard to skim through so, after reading it, I wanted to provide the high level summary as I understood it for others here.
How far are we from being able to model an entire mouse?
The last I heard was that someone could map all of a small worm, so a mouse is magnitudes more complicated than that. But compute power increases.
Also note that this isn't exactly news, it's been an ongoing research topic for a few years. Here is a research article from 2022: https://aacrjournals.org/cancerdiscovery/article/12/5/1356/6...
The biggest issue is that the mice we use for research typically have no or a highly depleted immune system. One of the biggest breakthroughs in the cancer field (IMO) is the development of humanized mice. These are mice that have had their immune system genes replaced with the human versions of these genes.
This is incredibly important for work like this where you’re studying cancer cell-immune cell interactions.
unfortunately, we need mice models for safety for now.
hopefully, computational models and personalized medicine will change this in the future.
1. Mice _love_ to get cancer naturally. If you have 100 mice, it's quite likely that around 20 of them will die within one year of cancer. This makes it difficult to extract useful signals. BTW, that's why if you see a study that a "chemical X results in cancer in mice", you should take that with a grain of salt.
2. Mice are small, so tumors are necessarily small too, with several orders of magnitude fewer cells than typical human tumors. So many drugs can just cure mice of cancer entirely, by killing cancerous cells too quickly to allow them to evolve resistance.
If you have 100 people, about 40 of them will be diagnosed with cancer over their lifetime (39/100 females and 41/100 males). Note "diagnosed with" is very different from "die" and "over lifetime" is not the same as "within one year", but the probability of people getting cancer naturally is high as well.
This all means that mice don't have a good natural cancer-suppression machinery, and this in turn makes them somewhat awkward to use to discover new treatments.
It’s easy to feel cynical when so many things seem like they get stuck for ages in trials and never make it to an actual treatment, but modern medicine is truly amazing. I have family who are sadly no longer with us, but who likely would have been cured completely if they had developed the same cancer today.
> our finding showed a significant increase in breast cancer mortality rate in the world during the past 25 years ... Statistical analysis showed a significant increase for breast cancer mortality rate in all super regions, except for High-income super region. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745227/
and for women under 40:
> Female breast cancer mortality rates have stopped declining in women younger than 40 years, ending a trend that existed from 1987 to 2010. Conversely, mortality rates have continued to decline in women aged 40–79 years. https://pubs.rsna.org/doi/full/10.1148/radiol.2021203476
I think this paper explains it: https://pubmed.ncbi.nlm.nih.gov/27175568/ "the major factors that accounted for these favorable trends were progress in tobacco control and improvements in early detection and treatment"
I feel like the treatment progress for most metastatic solid cancers have not significantly improved. A significant improvement wouldn't be just improving overall survival by a year or so. What seems possible to achieve (someday soon perhaps) is making cancer either a manageable condition, like HIV now is, or curable.