Andrej Karpathy and Kim Isenberg highlight a five-week surge of breakthroughs across gene editing, oncology, and diagnostic AI

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This has quietly been a miracle month in medicine.

In the last 5 weeks we’ve got news on:

- retatrutide, the triple agonist GLP-1 from Lilly, basically melting fat and body-wide inflammation at record levels - RevMed’s new pancreatic cancer drug showing unprecedented abilities to extend life - small trial of a one-and-done PCSK9 gene editing therapy for slashing LDL cholesterol - Mayo’s AI-assisted radiology showing vastly improved cancer detection - this new therapy for metastatic solid tumors

This stuff is at varying levels of evidence. Retatrutide is ~100% on its way, other stuff needs more clinical trial data. But put it together and we’re maybe on the verge of majorly reducing the mortality of heart disease and cancer, the two leading causes of death in America.

Crémieux@cremieuxrecueil

This is actually insane.

97% of people taking the standard of care for metastatic solid tumor got worse by seven years.

But with lorlatinib, that number was only 45% in the same time!

This is an ENORMOUS jump in the quality of cancer care.

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Derek Thompson@DKThomp

@ben_golub @deanwball Oh damn is quietly another AI word?!

That’s genuinely sad for me—and for readers everywhere.

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Apoorv@apoorv3E

@DKThomp Need to stay alive and relatively fit for 10-15 years to benefit from the magic that's about to happen.

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Matthew Herper@matthewherper

Hey Derek, I'm fascinated by the sudden tone on X around the Verve gene editing data. A lot of people are suddenly seeing the company's vision. That's a complete reversal from a few years ago, when most people just got an ick from it.

This is cool! I have equipoise on this one! But... the fundamental argument was the same for Verve's previous entrant before it hit safety worries! We've got a long while to argue back and forth on this one, even though it IS super neat.

And, honestly, except for RevMed, anyone following could have told you most of this eight weeks ago.

What has changed in that time is there have been update's to X's Pheonix algorithm for deciding what posts get shown on X.

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Ben Smith@semaforben

@DKThomp I wonder what the cultural politics of a spike in life expectancy will be? "Deaths of despair" felt so true to people; I don't think we're going to see a similarly metaphorical interpretation (but positive) here ....

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Ben Golub@ben_golub

@DKThomp @deanwball How are you feeling about the word quietly having quietly been killed

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Max Tyler@CoachMaxTyler

@DKThomp GLP-1 agonists are doing what we told people diet and exercise could do for decades. The irony: the same stress and cortisol that drives obesity also blunts the body's natural GLP-1 response. Fix the stress first, and the biology follows.

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Jesse Morse, M.D.@DrJesseMorse

@DKThomp I did a deep dive on what the data shows for Retatrutide if you’re interested

https://substack.com/@drjessemorse/note/p-198830784?r=ntnvf&utm_medium=ios&utm_source=notes-share-action

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Sahil🎧⚛️@TalkinIdeas

@DKThomp Retatrutide melting fat at record levels is wild, but I am more curious how fast these actually reach patients outside trial settings. The gap between promising data and real access is usually the bigger story.

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Eric Rottinghaus@RottinghausEric

@DKThomp You missed a big one. NTLA, first phase 3 in vivo gene editing trial reported. (HAE, a rare disease) Excellent results: look at how many events after the placebo crossover

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Chubby♨️@kimmonismus

source 1:

Nicholas Hornstein@GIMedOnc

#ASCO26

This one is special.

This is the hottest paper of 2026 and potentially in the history of pancreatic cancer.

Let’s dive in.

RASolute 302: Daraxonrasib vs investigator’s choice chemotherapy in previously treated metastatic pancreatic cancer Abstract LBA5 (soon!) Presentation: May 31, 2026, 3:21-3:33 PM CDT

For decades, pancreatic cancer has been where good ideas go to die.

We have optimized chemotherapy. We have sequenced chemotherapy. We have celebrated modest gains.

But the central driver of PDAC has always been sitting there in plain sight:

RAS.

More than 90% of pancreatic cancers have oncogenic RAS mutations, and until recently, we had essentially nothing direct to do about it.

Daraxonrasib is an oral RAS(ON) multiselective inhibitor targeting the active GTP-bound state of mutant and wild-type RAS.

And in RASolute 302, it delivered.

Quick hits:

📌 Phase 3 international randomized trial 500 patients with previously treated mPDAC Daraxonrasib vs investigator’s choice chemotherapy

🧬 RAS G12 population 91.8% of patients had RAS G12 mutations

📈 OS in RAS G12 population 13.2 vs 6.6 months HR 0.40 P<0.001

📈 OS in overall population 13.2 vs 6.7 months HR 0.40 P<0.001

📊 PFS in RAS G12 population 7.3 vs 3.5 months HR 0.45 P<0.001

📊 PFS in overall population 7.2 vs 3.6 months HR 0.49 P<0.001

🔥 12-month OS Overall population: 53.2% vs 17.3%

⚠️ Toxicity matters, but this was not just more efficacy for more toxicity Grade ≥3 AEs: 61.8% vs 69.6% TRAEs leading to discontinuation: 1.2% vs 11.2%

This is the kind of survival curve we almost never get to see in pancreatic cancer.

This validates RAS(ON) inhibition in the most RAS-addicted major cancer. It takes a target we have talked about for decades and turns it into a clinically meaningful survival benefit in a randomized phase 3 trial.

The next questions come fast: 1L combinations, maintenance, perioperative disease, sequencing, resistance, toxicity management, and whether this becomes a new backbone.

RAS is here, and it couldn’t have come sooner.

https://www.nejm.org/doi/full/10.1056/NEJMoa2605555?query=featured_home

@TheGutonclab @UGrewalMD @TimothyJBrownMD @OncoAlert @Onco_Nexus @ASCO @NazliDizman @LauraAlderMD @DVAraujoMD @DrBarbiOnc @LauraEsfeller @FunchainMD @YGaritaonaindia @DrSAHaddad @jgong15 @iandresmeraz @SakditadMD @RamilaShilpakar @RohitBanwar @lungoncdoc

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Ilya Valmianski@valmianski

@DKThomp Is retatrutide anti-inflammatory better than tirzepatide?

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Clockwork@DownToBiscuits

@CodyLonning @DKThomp

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Michael Schossler, ACE-CPT@TheBodtrainer

@DKThomp Record fat loss. Record inflammation reduction. Still zero protocol for the muscle underneath. The breakthroughs are real. The gap is still the same.

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Cody Lonning@CodyLonning

@DKThomp We've known how to reduce the mortality of heart disease and cancer for hundreds, if not thousands, of years. And do it for free.

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Mike Cottone@M_Cottone

@DKThomp @ben_golub @deanwball It’s not just killed, it’s excommunicated.

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Piranga🌻@RRcandid

@DKThomp @deanwball It’s a little confusing to call lorlatinib “this new therapy for metastatic solid tumors”. It targets one very specific and fairly rare oncogene driver in lung cancer - ALK rearrangement. It’s a great drug for that small patient group, but it doesn’t work for most cancers.

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Matteo Battocchio@imbatmat

@DKThomp @Noahpinion @grok tell me about “Mayo’s AI-assisted radiology showing vastly improved cancer detection”

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Rai@RaiNausherwan

@DKThomp It would be interesting to ask the people on the ground in these fields how ai is helping them specifically with their work

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FPGuy@GuyFp52606

@apoorv3E @DKThomp Part of my thought process on this is the ability to feel good working out is why many individuals on the heavier side tend not to take the first steps. If weight loss medication takes the first steps for them, people may become more motivated!

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