[HN Gopher] Prostate cancer includes two different evotypes
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Prostate cancer includes two different evotypes
Author : panabee
Score : 115 points
Date : 2024-03-13 20:17 UTC (2 hours ago)
(HTM) web link (www.ox.ac.uk)
(TXT) w3m dump (www.ox.ac.uk)
| skywhopper wrote:
| Kudos for this identification, but at this point, calling the use
| of neural networks in statistical work "AI" is misleading at
| best. I know it won't stop because it gets attention to claim
| "AI", but it's really depressing. Ultimately it's not really any
| different than all the talk about "mechanical brains" in the 50s,
| but it's just really tiresome.
| badRNG wrote:
| I think the average person can safely call "the use of neural
| networks in statistical work" AI.
| johnmaguire wrote:
| It's technically correct, but AI has become such an
| overloaded term that it's impossible to know it refers to
| "the use of neural networks" without explicitly saying so. So
| you know, maybe just say that?
| adw wrote:
| This debate is a classic. AI has always been an overloaded
| term and more of a marketing signifier than anything else.
|
| The rule of thumb is, historically, "something is AI while
| it doesn't work". Originally, techniques like A* search
| were regarded as AI; they definitely wouldn't be now.
| Information retrieval, similarly. "Machine learning", as a
| brand, was an effort to get statistical techniques (like
| neural networks, though at the time it was more "linear
| regression and random forests") out from under the AI
| stigma; AI was "the thing that doesn't work".
|
| But we're culturally optimistic about AI's prospects again,
| so all the machine learning work is merrily being rebranded
| as AI. The wheel will turn again, eventually.
| eichin wrote:
| ... and once it works, it "earns" a name of its own, at
| least among people actually doing it. Even in 2024 there
| are Machine Learning Conferences of note.
| whelp_24 wrote:
| Should the term AI just not be used until we have a skynet
| level ai?
| Filligree wrote:
| No, it should only be used about things that don't exist.
| outworlder wrote:
| > calling the use of neural networks in statistical work "AI"
| is misleading at best.
|
| Neural Networks are not considered AI anymore?
|
| That just reinforces my thesis that "AI" is an ever sliding
| window that means "something we don't yet have". Voice
| recognition used to be firmly in the "AI" camp and received
| grants from even the military. Now we have that on wrist
| watches (admittedly with some computation offloaded) and nobody
| cares. Expert systems were once very much "AI".
|
| LLMs will suffer the same treatment pretty soon. Just wait.
| depereo wrote:
| Another entry in the 'marketing and technical terms don't
| mean the same thing despite using the same words' saga.
| dartos wrote:
| The current usage of AI is a rather new market term.
|
| Where would you draw the line? Is prediction via linear
| regression AI?
|
| Also language is fuzzy and fluid, get used to it.
| Jensson wrote:
| It was called machine learning 10 years ago since AI had
| bad connotations, but today people have forgotten and call
| it all AI again.
| beeboobaa wrote:
| AI has always meant Artificial Intelligence. Intelligent and
| capable of learning, like a person.
|
| LLMs are not AI.
| outworlder wrote:
| > LLMs are not AI.
|
| Neither are neural networks, by that definition. Or
| 'machine learning' in general. They all have been called
| "AI" at different points in time. Even expert systems -
| that are glorified IF statements - they were supposed to
| replace doctors.
| Jensson wrote:
| People thought those techniques would ultimately become
| something intelligent, so AI, but they fizzled out. That
| isn't the doubters moving the goalposts, that is the
| optimists moving the goal posts always thinking what we
| have now is the golden ticket to truly intelligent
| systems.
| readthenotes1 wrote:
| Some people are incapable of learning. Therefore, LLMs are
| AI?
|
| As far as I recall, the turing test was developed long ago
| to give a practical answer to what was and was not
| practically artificial intelligence because the debate over
| the definition is much older than we are
| kristov wrote:
| I think the Turing test is subjective, because the result
| depends on who was giving the test and for how long.
| kromem wrote:
| Pretty soon? I already regularly see people proudly stating
| that LLMs "aren't really AI" and just "a Markov chain" (yeah
| sure, let's ignore the self-attention mechanism of
| transformers which violate the Markov property).
|
| For the sake of my sanity I've just started tuning out what
| anyone says about AI outside of specialist spaces and forums.
| I welcome educated disagreement from my positions, but I
| really can't take the antivaxx equivalent in machine learning
| anymore.
| mort96 wrote:
| What if we hold off on calling it AI until it shows sign of
| intelligence
| cwillu wrote:
| And what signs of intelligence are we looking for this
| year?
| jhbadger wrote:
| Chess was a major topic of AI research for decades
| because playing a good game of chess was seen as a sign
| of intelligence. Until computers started playing better
| than people and we decided it didn't count for some
| reason. It reminds me of the (real) quote by I.I. Rabi
| that got used in Nolan's movie when Rabi was frustrated
| with how the committee was minimizing the accomplishments
| of Oppenheimer: "We have an A-bomb! What more do you
| want, mermaids?"
| Jensson wrote:
| They chased chess since they thought if they could solve
| chess then AGI would be close. They were wrong, so then
| they moved the goalpost to something more complicated
| thinking that new thing would lead to AGI. Repeat
| forever.
|
| > we decided it didn't count for some reason
|
| Optimists did move their goals once you realized that
| solving chess actually didn't lead anywhere, and then
| they blamed the pessimists for moving even though
| pessimists mostly stayed still throughout these AI hype
| waves. It is funny that optimists constantly are wrong
| and have to move their goal like that, yes, but people
| tend to point the finger at the wrong people here.
|
| The AI winter came from AI optimists constantly moving
| the goalposts like that, constantly saying "we are almost
| there, the goal is just that next thing and we are
| basically done!". AI pessimists doesn't do that, all that
| came from the optimists that tried to get more funding.
|
| And we see that exact same thing play out today, a lot of
| AI optimists clamoring for massive amounts of money
| because they are close to AGI, just like what we have
| seen in the past. Maybe they are right this time, but
| this time just like back then it is those optimists that
| are setting and moving the goal posts.
| jijijijij wrote:
| Maybe it's a good indicator of misuse when the paper didn't
| mention 'AI', or 'intelligence' once.
|
| > my thesis that "AI" is an ever sliding window that means
| "something we don't yet have
|
| Or maybe it's the sliding window of "well, turns out this
| ain't it, there is more to intelligence than we wanted it to
| be".
|
| If everything is intelligent, nothing is. If you define
| pattern recognition as intelligence, you'd be challenged to
| find unintelligent lifeforms, for example. You haven't
| learned to recognize faces, you are literally born with this
| ability. And well, life at least has agency. Is evolution
| itself intelligent? What about water slowly wearing down rock
| into canyons?
| lja wrote:
| The taxonomy of AI is the following:
|
| AI
|
| -> machine learning
|
| ...-> supervised
|
| ........-> neural networks
|
| ...-> unsupervised
|
| ...-> reinforcement
|
| -> massive if/then statements
|
| -> ...
|
| That is to say NN falls under AI but everything falls into AI.
| p1esk wrote:
| Where did you pull this "taxonomy" from?
| peteradio wrote:
| Jo mommas bhole
| nonameiguess wrote:
| It implies agency on the part of the software that doesn't
| exist. It should really just say "researchers ran some math
| calculations and found X." The fact that the math runs on a
| computer and involves the use of functions that were found by
| heuristic-guided search using a function estimator, instead of
| human scientists finding them from first principles, is surely
| relevant in some way, but this has been the case for at least a
| century since Einstein's field laws required the use of
| numerical approximations of PDE solutions to compute gravity at
| a point, probably longer.
|
| I don't want to say there is no qualitative difference between
| what the PDE solvers of 1910 could do and what a GPT can do,
| but until we don't need scientists running the software at all
| and it can do decide to do this all on its own and know what to
| do and how to interpret it, it feels misleading to use
| terminology like "AI" that in the public consciousness has
| always meant full autonomy. It's going to make people think
| someone just told a computer "hey, go do science" and it
| figured this out.
| leesec wrote:
| Why would it be depressing? Who cares
| johnnyanmac wrote:
| taking credit from the drivers of tools to give credit to the
| tools themselves as PR? Yes, depressing. No one says "Unreal
| Engine Presents Final Fantasy VII". It's an important tool
| but not the creative mind behind the work.
| golemotron wrote:
| Because regulating "AI" has the potential to encompass all
| software development. Many programs act as decision support.
| From the outside there's little difference between an
| application that uses conventional programming, ML, RNNs, or
| GPT.
| advael wrote:
| I mean. "AI" has meant "whatever shiny new computer thing is
| hot right now" in both common vernacular and every academic
| field besides AI research basically since the term was
| coined...
| meindnoch wrote:
| In PR materials, AI = computers were involved
| hawski wrote:
| That's a problem with the term now. Whenever there is a PR
| statement of using AI it does not have much meaning attached
| to it. Sometimes even simple algorithms are called AI, if
| there is a bit of statistics involved even more. I liked the
| term machine learning, because now with AI-everything I don't
| really know what it is about.
| Aloisius wrote:
| John McCarthy coined the term AI in 1955 for a research project
| that included NN. He then founded the MIT AI Project (later AI
| Lab) with one of the researchers who joined the project, Marvin
| Minsky, who also had created the first NN in 1951.
|
| If NNs aren't AI, what is?
|
| http://jmc.stanford.edu/articles/dartmouth/dartmouth.pdf
| krisoft wrote:
| > but it's really depressing
|
| Why do you feel it depressing?
| whalesalad wrote:
| I thought this was pretty obvious? "Cancer" is not a thing, its a
| billion different things that happen differently in every single
| patient.
| renewiltord wrote:
| Thought I'd include the first line of the article:
|
| > _A Cancer Research UK-funded study, published in Cell
| Genomics, has revealed that prostate cancer, which affects one
| in eight men in their lifetime, includes two different subtypes
| termed evotypes._
|
| In some cosmic sense, the number "one billion" and the number
| "two" are the same, I suppose.
| whalesalad wrote:
| and in a year we'll have a new report: "foo bar genomics has
| revealed that prostate cancer includes 3 new evotypes"
|
| it's all just mutations and there is no upper bound on the
| number of mutations that can exist
| luqtas wrote:
| it's completely impressive how hackers here are multi-field
| specialists
| dudul wrote:
| I'm always amazed to see all these "well actually" comments
| on every single post, regardless of the topic :)
| eig wrote:
| While the parent commenter did exaggerate, they are correct
| in their idea. You could subclassify cancers all the way down
| to individual gene mutations, and even then there is
| heterogeny within the cancer itself.
|
| Medicine tries to draw boundaries where different therapies
| help differently or where there is different pathophysiology
| going on. The article was able to draw one such additional
| boundary. Its relevance is yet to be confirmed with its
| phenotype or druggability.
| purkka wrote:
| I'd guess what they mean is there are two clusters with some
| clear distinguishing properties, and perhaps some resulting
| implications for treatment.
| mr_toad wrote:
| Yes but this is true of nearly every illness, and it's true of
| natural phenomena in general, and it's true of most problems in
| statistical classification.
|
| But we still like to classify things, because it often has
| predictive power and informs treatment.
| f6v wrote:
| Ok, it's "obvious". Now find good drug targets. Yeah, you can't
| before you quantify all the "obvious" things. The actual
| patient data and derived insights are precious.
| bnjemian wrote:
| Yes, that's somewhat true, but in practice we have subtypes. As
| a counterfactual to that assertion, if it were meaningfully a
| billion different things, then we would need a billion highly
| precise treatments. Yet, we've managed to do decently with
| relatively few.
| panabee wrote:
| paper link: https://www.cell.com/cell-
| genomics/fulltext/S2666-979X(24)00...
| up2isomorphism wrote:
| No, at least in this case, human reveals something, not "AI".
| Unfortunately people need to use 'AI' to get some attention (no
| pun intended).
| aftbit wrote:
| Not to be rude or anything, but .... no duh? This is why looking
| for a "cure for cancer" is a bit nonsensical. There are many
| different ways for cell division to go wrong. Prostate cancer is
| just a cancer that affects the prostate. There's no reason to
| assume there would be one pathology for that.
| AlecSchueler wrote:
| It's one thing to intuit something but it's another to actually
| show it.
| fridder wrote:
| There is still a lot we do not know about why some prostate
| cancers grow slowly and are effectively benign and some are
| viciously malignant. This split leads some health practitioners
| to either relax or ignore screening guidelines. Being able to
| better narrow things down so we can avoid overly aggressive
| treatment while at the same time being appropriately aggressive
| for those that have more malignant variants. (BTW, this is not
| just theoretical for me)
| jeremyjh wrote:
| You are responding to the headline and not the content of the
| study. Yes, science headlines are stupid clickbait.
| f6v wrote:
| It's not that you're wrong, but you miss the depth of the
| issue. Yes, we know that people are different and there're many
| redundant pathways, and every poor bastard probably has his own
| mutation, etc.
|
| But we need to actually identify the mechanisms, describe them
| in a lot of detail, and look for very specific biomarkers.
| That's what "personalized medicine" is going to be.
|
| It's extremely difficult to put a study like this together. So
| many parts can go wrong. So it's an achievement not just for
| scientists who published in a good journal, but for the whole
| humanity.
| lr4444lr wrote:
| IANAD, but the early and ongoing successes of immunotherapy
| across a wide variety of cancers suggests that your
| characterization of this effort as "nonsensical" is cynically
| oversimplified, if not wrong.
| dataangel wrote:
| Isn't it the case that there are a near infinite number of forms
| of cancer for any organ? Any combination of mutations that causes
| unrestricted growth right? So how can it just be 2 forms?
| f6v wrote:
| There're redundant pathways, but it's not a million. I guess
| different mutations can converge to a common phenotype. And in
| any case, what you present in a study is kind of like a model
| that you derive from the data. You can probably go deeper, but
| you'd need more patients/more resources.
| bnjemian wrote:
| In principle, yes, in practice, no; real-world mutations are
| (more often than not) non-random and their frequencies can be
| affected by a variety of factors. For example, the location of
| the mutated gene or region within the bundled chromatin
| structure inside the cell nucleus (this structure is highly
| conserved into what are known as topologically associated
| domains, or TADs), or the interaction between a region of DNA
| and cellular machinery that increases the likelihood of some
| mutation. There are tons of examples.
|
| In practice, we've now molecularly characterized most well-
| studied cancers and know that they tend to have the same
| mutations. For example, certain DNMT3A mutations are very
| common in AML and the BCR-ABL fusion protein in CML (and
| results from an interaction between chromosomes 9 and 22 that
| produces the mutant 'Philadelphia chromosome'). There are even
| a wide range of cancers that share similar patterns of
| mutations and fall under the umbrella of 'RAS-opathies', which
| all exhibit some kind of mutation in a subset of genes on a
| specific pathway related to cell differentiation and growth.
| Examples include certain subtypes of colon cancer, lung cancer,
| melanoma, among many others.
|
| More generally, when a cancer is subtyped, that subtyping is
| always done with respect to some quantifiable biological trait
| or clinical endpoint and - as you've hinted - that subtyping is
| commonly a statistical assessment. Each cancer is unique and,
| even within an individual cancer, we have clonal subpopulations
| - groups of cells with differing mutations, characteristics,
| and behaviors. That's one of the reasons treating cancer can be
| so challenging; even if we eliminate one clonal population
| entirely, another resistant group may take its place. The
| implication is that cancers that emerge with post-treatment
| relapse are often 1. more or completely resistant to the
| original therapy, and 2. exhibit different behaviors and
| resistance, often to the detriment of the patient's outcome.
| molticrystal wrote:
| I think there is a difference in the infinite such as the
| example of monkeys typing Shakespeare, and the most vulnerable
| and likely areas to cause cancer which are what need to be
| focused on. In this specific, particular, and very likely for
| most people case it seems settle into 2 subtypes.
| o11c wrote:
| If you weld 2 sticks of metal together end to end, then bash
| them on the ground, they're likely to break at the weld. Insert
| additional physical examples here.
|
| Likewise DNA is likely to break (and fail to be corrected) at
| particular points. Some of those points cause cancer, but
| there's only a finite set of those points since DNA is largely
| identical across all humans. Additionally, even if the failure
| is slightly to one side of the expected break, it usually shows
| the same symptom.
| eig wrote:
| You could theoretically subclassify cancers all the way down to
| individual gene mutations, and even then there is heterogeny
| within one cancer itself. That is the idea behind "personalized
| medicine" though it's being distorted by hype.
|
| However, medicine is practical, and tries to draw boundaries
| where different therapies help differently or where there are
| different pathophysiology going on.
|
| The article was able to draw a new additional boundary. Its
| relevance is yet to be confirmed with its phenotype or
| druggability. If it turns out to be useful either in predicting
| therapy or outcome, it'll stick and oncologists will learn it.
|
| This process has already been repeated a lot in the
| hematological cancers, where previously cancers like "Hodgkin's
| lymphoma" have been subdivided as we made new treatments and
| discovered the individual pathways.
| herodotus wrote:
| The article itself never uses the term "AI" or "Artificial
| Intelligence". They do mention the use of a Neural Network as one
| part of their attempt to help find commonalities in their data
| set. It is too bad that the Oxford University press person chose
| to use that word in the title and in the article - badly (in my
| opinion) characterizing the work.
| staplers wrote:
| Probably institutional grant fishing.
| crispycas12 wrote:
| Ok very quick notes
|
| * Prostate cancers are known to have a wide spectrum of outcomes.
|
| * Stage IV (metastatic) disease tends to have genetic testing.
| These panels tend to be on the order of a few hundred genes to
| 1000s of genes.
|
| * Classically prostate cancer is driven by androgen receptor
| upregulation. Disease progression is often due to the disease
| overcoming treatment with antiandrogenic such as enzalutamide.
|
| Correction: enzalutamide was designed to overcome castrate
| resistant prostate cancer. abiraterone would have been more
| appropriate to bring up here.
|
| * Upon review of NCCN guidelines: there are two main genetic
| indicators for targeted therapies. Both of these mutations are
| indicated for germline and somatic contexts: BRCA1/2 for parp
| inhibition and dMMR/MSI-H for pembrolizumab
|
| o Note that there are some somatic mutations with HRD pathway
| that are indicated for treatment. But that is only if they are
| somatic
|
| * This study aims to figure out the etiology of the disease in an
| evolutionary manner. That is what are the key events that lead to
| oncogenesis.
|
| edit note: the word that escaped me was epistasic given that we
| are looking into the nuts and bolts cause and effects of
| different mutations.
|
| edit note 2: I'm going to be honest, most of the time I've read
| about prostate cancer is in the metastatic setting and thus it
| has already become castrate resistant. Abiraterone is also meant
| to aid in sensitizing castrate resistant prostate cancer. Let's
| just say androgen deprivation therapy for now. On the other hand,
| I hope this was instructive in showing how important AR is as a
| pathway for prostate cancer
|
| * Quick thought: this could be useful if this matches with
| molecular screening in earlier stage disease. If we can reliable
| map out which chain of events (tumor suppressor loss of function
| mutations/ gain of function mutations for oncogenes, chromosomal
| level mutations) lead to more aggressive disease, we can inform
| changes in surveillance and earlier/ more aggressive treatment.
|
| * Granted this isn't too out there, tissues cores are taken out
| to begin with to get initial snapshot into how aggressive disease
| (it's how you get the Gleason score after all).
|
| * Regarding switching pathways, that's not too crazy given
| neuroendocrine transformations exist in prostate + lung cancer
| stergios wrote:
| Gleason scores already designate 5 different types/categories of
| PaC, and this score strongly influences what type of barbaric
| treatment one will receive.
|
| I hope their findings help discovery of humane immunotherapy's.
| sroussey wrote:
| My father was diagnosed with a Gleason score of 10 this year.
|
| When it's this bad, ironically some barbaric options are off
| the table.
| kmbfjr wrote:
| I was just diagnosed with 7/7.5 Gleason score prostate cancer
| (adenocarcinoma).
|
| The barbarians are cutting it out in 4 weeks.
|
| A life of pissing my pants beats dying before retirement.
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