from Hacker News

Prostate cancer includes two different evotypes

by panabee on 3/13/24, 8:17 PM with 84 comments

  • by i000 on 3/13/24, 11:33 PM

    I tried to dissect this paper on my recent 6h flight. Despite a decade of research in prostate cancer genomics I could not figure out what is going on. the results are both vague and at odds with established knowledge. the computational approaches complex and impenetrable. I sent it to my students as an example of computational over cooking.

  • by crispycas12 on 3/13/24, 10:04 PM

    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

  • by dataangel on 3/13/24, 9:32 PM

    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?

  • by killjoywashere on 3/13/24, 11:58 PM

    </pull paper>

    > Despite the reduced dimensionality of the feature representation, application of standard clustering methods remains problematic due to the high dimension of features (30) relative to the sample size (159). To mitigate this,

    and I'm done.

  • by panabee on 3/13/24, 8:48 PM

  • by stergios on 3/13/24, 10:26 PM

    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.

  • by skywhopper on 3/13/24, 8:43 PM

    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.

  • by up2isomorphism on 3/13/24, 9:04 PM

    No, at least in this case, human reveals something, not "AI". Unfortunately people need to use 'AI' to get some attention (no pun intended).

  • by herodotus on 3/13/24, 9:41 PM

    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.

  • by whalesalad on 3/13/24, 8:48 PM

    I thought this was pretty obvious? "Cancer" is not a thing, its a billion different things that happen differently in every single patient.

  • by aftbit on 3/13/24, 9:14 PM

    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.