Wungki Park, MD MS

1/n Now published in @NatureMedicine : The phase 2 #POLAR trial of pembrolizumab + olaparib maintenance in metastatic pancreatic cancer. @CpcrMsk @MSKCancerCenter @MSK_DeptOfMed @PICIatMSK rdcu.be/e9WmJ

Dr. Hidalgo @DrMhidalgo, the director of @nyuniversity Grossman SOM Gastrointestinal Cancer Center, put it bluntly: “This is the most important clinical trial data in pancreatic cancer, ever.” Wungki Park (@CentralParkWMD), @MSKCancerCenter oncologist who was involved in the clinical trial, told me that he’s gotten goosebumps while reviewing his patients’ responses to the drug. Park sees this drug as the start of a new chapter in pancreatic cancer treatment: one where doctors have more to offer their patients than just chemo, and researchers get better and better at designing treatments that can shut down these tumors. #KRAS #RAS @KRASKickers @NatPancFdn @PanCAN @Pankind_Aus @lustgartenfdn bloomberg.com/opinion/articl…

@DrMhidalgo, the director of @NYU Grossman SOM Gastrointestinal Cancer Center, put it bluntly: “This is the most important clinical trial data in pancreatic cancer, ever.” @CentralParkWMD, a @MSKCancerCenter oncologist who was involved in the clinical trial, told me that he’s gotten goosebumps while reviewing his patients’ responses to the drug. Park sees this drug as the start of a new chapter in pancreatic cancer treatment: one where doctors have more to offer their patients than just chemo, and researchers get better and better at designing treatments that can shut down these tumors. #KRAS #RAS @KRASKickers @PanCAN @NatPancFdn @lustgartenfdn bloomberg.com/opinion/articl…

Fascinating~ The next moves...♟️🏁

Landscape of #PancreaticCancer treatment is changing! @EileenMOReilly, a gastrointestinal medical oncologist @MSK_DeptOfMedwho was involved with the studies on daraxonrasib, says the encouraging findings about daraxonrasib "hopefully set the stage for building on targeted therapy as a major backbone for the treatment of pancreas cancer, and a key goal now is to build and extend these results in all stages." “I’ve already told my colleagues that today is an inflection point that if things stays positive, everything should change,” says Dr. Wungki Park @CentralParkWMD, a pancreatic cancer specialist @MSKCancerCenter, who was involved in the early human trials of daraxonrasib. “There will be pre-daraxonrasib and post-daraxonrasib. This is a really, really good outcome.” Congratulations to Elraglusib team! nature.com/articles/s4159… Devalingam Mahalingam,@rachnatshroffBenedito Carneiro and@GIcancerDoc time.com/article/2026/0…

The @DanaFarber RAS Center is a patient resource for KRAS G12C, KRAS G12D, and pan-RAS/pan-KRAS trial options. @DanaFarberNews

RevMed just doubled overall survival in pancreatic cancer by using CypA-targeting molecular glues to potently drug oncogenic KRAS-ON, long deemed untouchable. One funny thing is that probably the most fundamental insight for daraxonrasib sits in a PNAS paper that's been cited merely 84 times. This showed that molecular glues can coax an endogenous protein to wrap itself around utterly featureless surface. The other is a 2017 Cell Reports paper (just 68 citations) on how Sanglifehrin A can be used to repurpose CypA's surface. A lot of the game-changing stuff seems niche and unglamorous at first. Greg Verdine is having a chembio Annus Mirabilis for his 2025-2026 streak: FOG-001, Daraxonrasib. He provided much of the foundational conceptual work behind taking out both Beta-catenin and KRAS*. *of course many others contributed immensely, but let's give some credit where credit is due!

An #AACR24 simultaneous publication flashback - ICYMI in @CD_AACR: Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 (now known as #daraxonrasib) in RAS-Driven Cancers doi.org/10.1158/2159-8…

@GarridoLagunaMD @KRASKickers @letswinpc So happy to see things are moving and almost shocked how close the phase I survival data is to this phase three data. Looking forward to reading the full presentation and paper.

@KRASKickers @letswinpc game changer for our pancreatic cancer patients. Daraxonrasib doubles overall survival 13 vs 6.7 months HR 0.4 (p<0.0001). Can’t wait to see this available to our patients all over the world ir.revmed.com/news-releases/…

That Phase 3 overall survival data is in second line #PancreaticCancer which makes the numbers even more astounding. I cannot recall any other example in pancreatic cancer when OS in a Phase 3 trial basically doubled over existing standard of care. statnews.com/2026/04/13/rev…

@RueschCenter @coffman_kelley @FASinicropeMD @EileenMOReilly Thank you @coffman_kelley for highlighting the study. Very insightful review of other trials too!

In the recent GI publication search,@coffman_kelley, M.D., highlighted new research by Wungki Park, M.D. (@CentralParkWMD); Jonathan W. Goldman, M.D.; @FASinicropeMD; Christopher H. Lieu, M.D.; @EileenMOReilly, M.D.; Jeffrey A. Meyerhardt, M.D.; Esther N Dekker, M.D.; @BasGrootKoerkam, M.D., Ph.D, and others, published in @NEJM and @JNCI_Now. Learn more: youtu.be/mzaSC7Xsfa8?si…

New drugs take aim at one of cancer’s deadliest mutations “You can actually re-educate the cell: ‘hey, this is disposable, just remove it’” nature.com/articles/d4158…

Relevant to Setidegrasib and the G12D targeting problem: KRAS G12D sits at d_ij=1.028 on a geometric coherence probe (frozen, zero parameters, PDB-measured). That is the boundary zone — the GTPase is abolished so the protein is permanently stuck there with no natural return drive. Covalent G12C inhibitors try to shift the address: Sotorasib: 1.095→2.448 (+1.35, toward WT) — 8 mo PFS Adagrasib: 1.095→0.802 (-0.29, deeper lock) — 8 mo PFS Opposite geometric directions. Same clinical outcome. Bypass dominates both. A degrader sidesteps the geometry problem entirely — you don’t need to move the address if you remove the protein. That may be why degraders are the right strategy for G12D specifically: the boundary-zone address has no covalent handle and no natural return drive, so geometric correction is harder than elimination. Geometric triage table for RAS family available if useful.

🧬 KRAS G12D: from “undruggable” to targetable 📊 Phase I – setidegrasib 🫁 NSCLC → ORR 36% | mPFS 8.3 mo | mOS NE 🧠 Pancreas → ORR 24% | mPFS 3 mo | mOS 10.3 mo ⚠️ Manageable toxicity 🚀 First meaningful signal in KRAS G12D 🔗 doi.org/10.1056/NEJMoa… @OncoAlert

Setidegrasib (NEJM 2026, Phase 1) degrades KRAS G12D. NSCLC: ORR 36%, PFS 8.3 mo Pancreas: ORR 24% A big step toward drugging KRAS G12D. #MVOnco #ELCC2026

Research to be presented at #AACR26 next week x.com/KRASKickers/st…

@jmsongmd, @MuzumdarLab is amazing you should check out at Yale!

🚨Check out this interesting work by @MuzumdarLab the true physician scientist studying endocrine effect on carcinogenesis in the exocrine system. This may explain why obese patients develop pancreatic cancer! Would love to hear your next clinical question and next impactful aim based on this?

@MuzumdarLab @YaleCancer @YaleGenetics @CancerYale Congratulations 🎉🎊🎈🍾 @MuzumdarLab this is so interesting! Amazing to see this work finally on paper. So we now have more clue on why obese patients develop pancreatic cancer, based on this fantastic work. So what do you plan to do now?

📢 New paper alert 🚨 We found that β cells are bona fide drivers of #obesity-associated #PancreaticCancer progression → targeting the #endocrine pancreas might prevent #exocrine cancer. 🔑 #CancerBiology. @YaleCancer @YaleGenetics @CancerYale 🧵 👇🏾 nature.com/articles/s4146…