<rss version="2.0" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:atom="http://www.w3.org/2005/Atom"><channel><title>Hacker News: HedonicEscal8r</title><link>https://news.ycombinator.com/user?id=HedonicEscal8r</link><description>Hacker News RSS</description><docs>https://hnrss.org/</docs><generator>hnrss v2.1.1</generator><lastBuildDate>Fri, 28 Aug 2026 09:51:51 +0000</lastBuildDate><atom:link href="https://hnrss.org/user?id=HedonicEscal8r" rel="self" type="application/rss+xml"></atom:link><item><title><![CDATA[New comment by HedonicEscal8r in "FDA approves first in class targeted therapy for metastatic pancreatic cancer"]]></title><description><![CDATA[
<p>mRNA vaccines are being studied for pancreatic cancer. To quote a post I wrote in April:<p>> 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.<p>> 7/8 responders (87.5%) survived 6 years after surgery, 2/8 nonresponders survived (25%).<p>> AACR meeting notes <a href="https://www.aacr.org/blog/2026/04/20/live-updates-from-the-aacr-annual-meeting-2026-monday-april-20/" rel="nofollow">https://www.aacr.org/blog/2026/04/20/live-updates-from-the-a...</a><p>> 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.<p>> Source on survival rates <a href="https://www.pancreaticcancer.org.uk/information/just-diagnosed-with-pancreatic-cancer/if-you-can-have-surgery-to-remove-the-cancer-early-pancreatic-cancer/prognosis-if-you-can-have-surgery/" rel="nofollow">https://www.pancreaticcancer.org.uk/information/just-diagnos...</a><p>Still early, unfortunately, so it will be a while before we see more updates.</p>
]]></description><pubDate>Fri, 28 Aug 2026 03:23:38 +0000</pubDate><link>https://news.ycombinator.com/item?id=49473990</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49473990</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49473990</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "FDA approves first in class targeted therapy for metastatic pancreatic cancer"]]></title><description><![CDATA[
<p>It can be disappointing to see that even a successful drug, like this one, is "only" extending life expectancy from 6.7 months to 13.2. But this is what the first steps towards a cure look like.<p>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.<p>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.</p>
]]></description><pubDate>Wed, 26 Aug 2026 20:00:28 +0000</pubDate><link>https://news.ycombinator.com/item?id=49454991</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49454991</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49454991</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "Why is Anthropic's public writing style so unlike Claude's?"]]></title><description><![CDATA[
<p>The phrase is, "don't get high on your own supply."</p>
]]></description><pubDate>Mon, 24 Aug 2026 16:57:03 +0000</pubDate><link>https://news.ycombinator.com/item?id=49422630</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49422630</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49422630</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "A complex structure on S^6 [pdf]"]]></title><description><![CDATA[
<p>Tax law is not arbitrarily complicated, and unexpected edge cases are settled by human judges, not by mathematical proofs.</p>
]]></description><pubDate>Mon, 24 Aug 2026 01:18:30 +0000</pubDate><link>https://news.ycombinator.com/item?id=49414250</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49414250</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49414250</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "Moderna reports first positive Phase 3 for mRNA neoantigen therapy in melanoma"]]></title><description><![CDATA[
<p>This is not quite correct. An mRNA vaccine that creates healthy antigens will fail because it won't do anything, not because it will trigger autoimmune issues. Your cells are already covered in normal antigens, and your immune system already knows to not attack them. It is true that it is difficult to find the right antigens to target, but the reasons for that are more complicated.</p>
]]></description><pubDate>Fri, 21 Aug 2026 21:08:07 +0000</pubDate><link>https://news.ycombinator.com/item?id=49393808</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49393808</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49393808</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "Moderna reports first positive Phase 3 for mRNA neoantigen therapy in melanoma"]]></title><description><![CDATA[
<p>You're confusing me with u/addisonl. Please check usernames before accusing people of trying to "silence the other side."<p>To quote a blog post I wrote on why we can be confident sun exposure causes cancer: "Green et al. (2011) conducted a 10-year study (n=1621) in Nambour, a town in Queensland, Australia. Participants were randomly assigned to daily or discretionary sunscreen application. After 10 years, 11 melanomas were found in the daily group and 22 in the discretionary group."<p>But you should read the full post for more context on why we have much better data than randomized controlled trials, and why correlation studies on this subject are nearly useless due to the impossibility of finding reliable proxy variables: <a href="https://hedonicescalator.substack.com/p/contra-byrnes-on-uv-and-cancer" rel="nofollow">https://hedonicescalator.substack.com/p/contra-byrnes-on-uv-...</a><p>Saying "some of the ingredients in US sunscreens are themselves associated with cancer" is meaningless without more specificity. As the meme goes, this HackerNews comment is known to the state of California to cause cancer: the bar for something to be "associated with cancer" is incredibly low. Are there any particular chemicals or chemical classes you were worried about?<p>And I will remind you that, in contrast, we are 100% sure that sunlight causes cancer. We know exactly what kinds of DNA damage it creates (chiefly cyclobutane pyrimidine dimers, which I discuss in my blog post) and we can find cancer-causing mutations in melanoma samples directly downstream of that damage (C->T mutations, for example, ones that disable the key p53 tumor suppressor gene). We know how this shit works! Are there some sunscreen formulas that might be dangerous? Possibly, I don't have them all memorized, but the solution is to find a different brand... not to instead expose yourself to one of the best-studied carcinogens around.</p>
]]></description><pubDate>Fri, 21 Aug 2026 03:51:10 +0000</pubDate><link>https://news.ycombinator.com/item?id=49383574</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49383574</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49383574</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "AI companies destroy physical books – let's scan rare books before it's too late"]]></title><description><![CDATA[
<p>If only this complaint was being posted by an organization ideologically opposed to copyright itself!</p>
]]></description><pubDate>Fri, 21 Aug 2026 03:29:56 +0000</pubDate><link>https://news.ycombinator.com/item?id=49383419</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49383419</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49383419</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "AI companies destroy physical books – let's scan rare books before it's too late"]]></title><description><![CDATA[
<p>The piracy organizations are playing 4D chess while everyone else is playing checkers. The irony of this entire situation - AI companies being legally required to shred books due to kafkaesque copyright laws, then used as a marketing tactic by Anna's Archive - is a work of art.<p>I support Anna's Archive, by the way. Information wants to be free.</p>
]]></description><pubDate>Fri, 21 Aug 2026 03:29:31 +0000</pubDate><link>https://news.ycombinator.com/item?id=49383415</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49383415</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49383415</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "Moderna reports first positive Phase 3 for mRNA neoantigen therapy in melanoma"]]></title><description><![CDATA[
<p>u/danjl was originally asking about "this class of drugs", which is more reasonably interpreted as referring to personalized mRNA vaccines rather than the much broader concept of (personalized or not) immunotherapy.<p>The comment is wrong because it's stupid. Just because we've known that personalized immunotherapy was a promising idea for a long time, and have been trying it with the limited tools we had (CAR T being the poster child, and while an incredible advancement for blood cancers and many other diseases, it is notoriously dangerous and expensive), does not mean we had the technology to accomplish it. Today's results are only possible because of recent advancements in multiple fields, and to respond with "they've tried immunotherapy for decades" is profoundly ignorant. You may as well say, "scientists have been trying to cure cancer for years."</p>
]]></description><pubDate>Wed, 19 Aug 2026 17:40:53 +0000</pubDate><link>https://news.ycombinator.com/item?id=49364670</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49364670</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49364670</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "Moderna reports first positive Phase 3 for mRNA neoantigen therapy in melanoma"]]></title><description><![CDATA[
<p>Yes, but OP said that in response to a comment attributing melanoma to sun exposure, in a conversation where nobody had brought up SCC or BCC. It's still a misleading comment, in my opinion.</p>
]]></description><pubDate>Wed, 19 Aug 2026 16:37:00 +0000</pubDate><link>https://news.ycombinator.com/item?id=49363821</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49363821</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49363821</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "Moderna reports first positive Phase 3 for mRNA neoantigen therapy in melanoma"]]></title><description><![CDATA[
<p>One of the leading problems is that we don't know how to pick the right neoantigens (mutant cancer proteins) which can trigger the optimal immune response.<p>Moderna used a simple heuristic, "how likely is this antigen to show up on the cell surface?" which makes sense, since an antigen has to show up on the cell surface for the immune system to see it. But there's so much missing from this model, and we just don't have enough data. Failures in clinical trials of mRNA vaccines may well be caused by this problem. (Yes, this is a good problem for AI, if we can get enough data).</p>
]]></description><pubDate>Wed, 19 Aug 2026 16:29:47 +0000</pubDate><link>https://news.ycombinator.com/item?id=49363717</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49363717</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49363717</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "Moderna reports first positive Phase 3 for mRNA neoantigen therapy in melanoma"]]></title><description><![CDATA[
<p>Interjecting with a fact. Moderna described the neoantigen immunogenicity prediction algorithm they used to design the vaccines as “a deterministic machine learning (ML) algorithm,” so it may be a small neural network or more traditional algorithm, probably not deep learning.</p>
]]></description><pubDate>Wed, 19 Aug 2026 16:21:53 +0000</pubDate><link>https://news.ycombinator.com/item?id=49363619</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49363619</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49363619</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "Moderna reports first positive Phase 3 for mRNA neoantigen therapy in melanoma"]]></title><description><![CDATA[
<p>Personalized mRNA vaccines are in fact, extremely new, and only made possible by recent advances across multiple fields. This comment reveals a total lack of basic understanding on this topic.</p>
]]></description><pubDate>Wed, 19 Aug 2026 16:18:27 +0000</pubDate><link>https://news.ycombinator.com/item?id=49363582</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49363582</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49363582</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "Moderna reports first positive Phase 3 for mRNA neoantigen therapy in melanoma"]]></title><description><![CDATA[
<p>Yes, mRNA vaccines are promising for many but not all cancer types, and there are many ongoing clinical trials. There's also a lot we yet don't know about how to design them.<p>Here's a great blog post on this, "How to build a cancer vaccine, and whether they will work this time": <a href="https://www.owlposting.com/p/how-to-build-a-cancer-vaccine-and" rel="nofollow">https://www.owlposting.com/p/how-to-build-a-cancer-vaccine-a...</a><p>Here's the blog post I wrote on personalized mRNA vaccines: <a href="https://hedonicescalator.substack.com/p/did-paul-conyngham-really-use-ai" rel="nofollow">https://hedonicescalator.substack.com/p/did-paul-conyngham-r...</a></p>
]]></description><pubDate>Wed, 19 Aug 2026 16:14:33 +0000</pubDate><link>https://news.ycombinator.com/item?id=49363534</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49363534</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49363534</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "Things That Used to Be Normal and Are Now a Luxury"]]></title><description><![CDATA[
<p>The night sky isn't dark. What you're looking for is cave darkness.</p>
]]></description><pubDate>Tue, 18 Aug 2026 16:18:08 +0000</pubDate><link>https://news.ycombinator.com/item?id=49348000</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49348000</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49348000</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "Will you have spent more of your life with computers than your family?"]]></title><description><![CDATA[
<p>If you think of your screen is a big glowy box of noise that fails to contribute to a good, meaningful life, that's a problem! Put better things on your screen.</p>
]]></description><pubDate>Mon, 17 Aug 2026 20:18:58 +0000</pubDate><link>https://news.ycombinator.com/item?id=49337010</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49337010</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49337010</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "First human trials of designer protein therapies stun US neuroscientists"]]></title><description><![CDATA[
<p>"Multiple controlled trials" is quite different from an under-the-table, privately funded bespoke therapy for a single patient.</p>
]]></description><pubDate>Sat, 15 Aug 2026 21:16:32 +0000</pubDate><link>https://news.ycombinator.com/item?id=49314418</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49314418</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49314418</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "Illinois just told every operating system to start reporting your kid's age"]]></title><description><![CDATA[
<p>If the kid's old enough to be hiding their internet history from their parents, they're old enough to have some privacy.</p>
]]></description><pubDate>Sun, 09 Aug 2026 07:08:33 +0000</pubDate><link>https://news.ycombinator.com/item?id=49229119</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49229119</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49229119</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "Has the New Cocaine Arrived?"]]></title><description><![CDATA[
<p>Not that I recommend being on 3-MMC at work, but it's just a matter of dosage. People take pharmaceutical doses of Adderall at work and 10x higher recreational doses at clubs.</p>
]]></description><pubDate>Sun, 02 Aug 2026 17:05:15 +0000</pubDate><link>https://news.ycombinator.com/item?id=49146261</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49146261</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49146261</guid></item><item><title><![CDATA[New comment by HedonicEscal8r in "Has the New Cocaine Arrived?"]]></title><description><![CDATA[
<p>The only common drugs that cause deadly withdrawals are alcohol and benzodiazepines. Opioid withdrawals are famously extremely unpleasant but not typically considered life-threatening.</p>
]]></description><pubDate>Sun, 02 Aug 2026 16:42:03 +0000</pubDate><link>https://news.ycombinator.com/item?id=49146054</link><dc:creator>HedonicEscal8r</dc:creator><comments>https://news.ycombinator.com/item?id=49146054</comments><guid isPermaLink="false">https://news.ycombinator.com/item?id=49146054</guid></item></channel></rss>