Top 5 Papers
#1
Source: AstraZeneca — Phase III press release | Authors: AstraZeneca / EMERALD-3 investigators (Llovet, Ducreux, et al.) | Published: May 2026 (topline)
Score: 14/20 — Base 6 (Phase 3 press release) + 3 (Phase III RCT) + 2 (PFS benefit) + 3 (new standard-of-care candidate for embolization-eligible HCC, first quadruplet to beat TACE in PFS).
AstraZeneca announced positive topline Phase III results from EMERALD-3: in 760 patients with unresectable hepatocellular carcinoma eligible for embolization across 171 sites in 22 countries (1:1:1 randomization to durvalumab + tremelimumab + lenvatinib + TACE vs durvalumab + tremelimumab + TACE [STRIDE+TACE] vs TACE alone), the quadruplet regimen significantly improved progression-free survival vs TACE alone — the trial's primary endpoint. The STRIDE + TACE arm also showed strong trends toward improved PFS and OS, though not formally tested at this interim. At the OS interim analysis, the quadruplet showed a trend toward OS improvement; follow-up continues for the key secondary endpoint. Safety was consistent with the known profile of each agent. Detailed data will be presented at an upcoming medical meeting. This is the first IO/IO + TKI + TACE quadruplet to beat TACE in a Phase III locoregional HCC trial — and it extends the EMERALD-1 (durva ± bev + TACE) signal into a substantially more active backbone.
Post angle: 🌍 EMERALD-3 — IO/IO + TKI + TACE beats TACE alone in embolization-eligible HCC. Durva + treme + lenvatinib + TACE: significant PFS win + OS trend. STRIDE + TACE also trending. The TACE-alone era in intermediate HCC is officially ending. #HCC #LiverCancer #GIOnc
#2
Source: New England Journal of Medicine (NEJM) | Authors: Wolpin BM, Park W, Garrido-Laguna I, Spira A, et al. (Revolution Medicines) | Published: NEJM 394(18):1790–1802 — May 7, 2026
Score: 17/20 — Base 10 (NEJM) + 2 (Phase 1/2) + 1 (RAS-mutation biomarker-selected) + 2 (clinically meaningful OS in a previously treated PDAC population) + 2 (multi-KOL X engagement — OncoAlert pinned post + DaisukeKotani repost).
The formal NEJM peer-reviewed publication of the daraxonrasib (RMC-6236) RAS(ON) multiselective inhibitor Phase 1/2 study. Among 168 patients with previously treated RAS-mutated PDAC, treatment-related AEs were reported in 96% (any grade) and 30% grade ≥3 — mostly rash, diarrhea, nausea, stomatitis/mucositis, vomiting, and fatigue. In 26 patients with KRAS G12 mutations treated with second-line daraxonrasib 300 mg (the selected Phase 3 dose), ORR was 35% (95% CI 17–56), median duration of response 8.2 months, median PFS 8.5 months, and median OS 13.1 months. Across G12/G13/Q61 mutations (n=38), ORR was 29% with median OS 15.6 months. These are best-in-class outcomes for 2L PDAC, where standard chemotherapy historically yields ~6 months OS — and they anchor the RASolute 302 Phase 3 readout headed for the ASCO 2026 Plenary on May 31. The accompanying NEJM editorial (Der & Yeh) frames daraxonrasib as the proof-of-concept that the RAS-mutant PDAC fortress is finally breakable.
Post angle: 🧬 NEJM finally publishes daraxonrasib (RMC-6236) full Phase 1/2 in 2L KRAS-mutant PDAC:
• KRAS G12 (n=26): ORR 35%, DoR 8.2 mo, PFS 8.5 mo, OS 13.1 mo
• G12/13/Q61 (n=38): OS 15.6 mo
• G3+ TRAEs 30%, mostly rash/GI
For a disease where 2L SoC delivers ~6-mo OS, this is generational. RASolute 302 ASCO Plenary May 31 next. #PDAC #KRAS #GIOnc #NEJM
#3
Source: Clinical & Translational Oncology | Authors: Moraes FCA, Rego LHRM, Rebelo TG, Matheus GTFU, Melo AC | Published: Clin Transl Oncol — May 12, 2026
Score: 8/20 — Base 5 (other journal) + 2 (meta-analysis) + 1 (biomarker-guided / precision implication — direct treatment-selection consequence).
Pooled meta-analysis of 3,515 patients across 20 studies of matched primary–metastatic gastric cancer HER2 testing. HER2-positive prevalence was 13% in primary tumors (95% CI 12–15%) versus 18% in metastatic lesions (95% CI 16–20%). Crucially, prevalence varied dramatically by metastatic site: 38% in lung metastases, 31% in liver metastases, 19% in lymph nodes, and only 7% in peritoneum. The implication is direct and practical — relying solely on the primary tumor HER2 status underestimates targetable HER2 positivity in advanced disease, particularly when liver- or lung-metastases-dominant patterns are present. With trastuzumab, T-DXd, zanidatamab, and now disitamab vedotin all in active development for HER2-positive gastric/GEJ cancer, the case for systematic metastatic re-biopsy at progression and at initial advanced-disease workup just got stronger.
Post angle: 📊 HER2 status in gastric cancer is NOT a primary-tumor decision:
• HER2+ primary: 13%
• HER2+ metastasis: 18%
• Lung mets: 38% HER2+
• Liver mets: 31% HER2+
• Peritoneum: 7% HER2+
Meta-analysis (n=3,515) makes the case for routine metastatic re-biopsy. With T-DXd, zanidatamab and DV all in play, this is treatment-decision-grade. #GastricCancer #HER2 #PrecisionOnc
#4
Source: Surgery | Authors: Vieira C, Silva M, Verma C, Kitano M, Court CM, McIntyre CA, Ecker BL, Parikh AA | Published: Surgery 196:110234 — May 11, 2026
Score: 8/20 — Base 5 (other journal) + 1 (retrospective / real-world) + 2 (OS benefit on adjusted analysis; HR 0.54 with both pre+post chemo).
Population-based analysis of the SEER-Medicare 2000–2020 cohort: among 42,235 patients with liver-only colorectal metastases, 3,752 (9%) underwent hepatectomy. Perioperative chemotherapy (defined as systemic therapy ≤6 mo before or ≤4 mo after surgery, or both) was given in 54% (14% preop only, 22% postop only, 18% both). Use modestly declined over time (OR 0.97/year, 95% CI 0.95–0.98). On multivariable analysis, perioperative chemotherapy was independently associated with improved overall survival, with the largest effect seen when both preop and postop chemo were given (HR 0.54, 95% CI 0.47–0.60, p<0.001). The 9% resection rate of all liver-only-metastatic patients tracks with literature, but the durable population-level OS signal — across two decades, with declining use over time — reinforces continued multimodal management even as biologic-era guidelines remain split. Limitations: residual confounding by indication is unavoidable in observational data, and the cohort skews older (Medicare).
Post angle: 🔪 SEER-Medicare 2000–2020: 3,752 hepatectomies for CRLM.
• 54% got perioperative chemo (declining over time)
• Periop chemo → HR 0.54 OS (pre+post combined)
• Pre-only HR also benefits, post-only HR benefits
Guidelines remain split, but real-world signal across 2 decades is consistent: don't drop the chemo bookends. #CRC #LiverMets #GIOnc
#5
Source: Gut | Authors: Liu J, Hou X, Li L, et al. (Tianjin Medical University Cancer Institute) | Published: Gut 75(6):1169–1185 — May 12, 2026
Score: 8/20 — Base 5 (Gut — Other tier in scoring system) + 1 (biomarker-guided / precision implication) + 2 (provides a clinically actionable combination strategy with a Phase-clinical-stage KRAS-G12D inhibitor).
Mechanism paper that solves a real clinical puzzle: zolbetuximab and other CLDN18.2-targeted therapies have modest efficacy in PDAC despite high CLDN18.2 expression. Using PDOs, humanized PDX, KPC mice, and KPC-Cldn18.2-KO mice, the authors show that mutant KRAS and hyperglycemia cooperatively drive O-GlcNAcylation of CLDN18.2 at residue T204, redistributing the protein from the membrane into the cytoplasm. This both reduces target accessibility for CLDN18.2-binding antibodies/CAR-T/ADCs and drives migration, invasion, and metastasis. Mechanistically, O-GlcNAc-modified CLDN18.2 loses PTP1B binding, gains tyrosine phosphorylation, and recruits PI3K via SH2 to activate AKT. Both genetic (T204A) and pharmacological blockade of O-GlcNAcylation restores CLDN18.2 membrane localization and suppresses tumor progression. Therapeutically, low-dose MRTX1133 (clinical-stage KRAS G12D inhibitor) reduces O-GlcNAcylation and synergizes with CLDN18.2-targeted therapy with minimal toxicity. A concrete, testable combination strategy for KRAS-mutant PDAC, where two of the most clinically promising therapeutic classes converge.
Post angle: 🎯 Why does CLDN18.2-targeted therapy stall in PDAC despite high expression?
New Gut paper: mutant KRAS + hyperglycemia O-GlcNAcylates CLDN18.2 at T204 → kicks it off the membrane → loss of target + pro-invasion signaling.
Fix: low-dose MRTX1133 (KRAS G12Di) restores membrane CLDN18.2 + synergizes. Trial-ready. #PDAC #KRAS #CLDN18 #PrecisionOnc
Additional Papers of Interest
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Revolution Medicines — Pivotal Phase III RASolute 302 of daraxonrasib vs SoC chemo in 2L KRAS-mutant metastatic PDAC met primary endpoints; full data to be presented at the ASCO 2026 Annual Meeting Plenary Session on May 31. Companion to today's NEJM Phase 1/2 publication.
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NEJM 394(18):1857–1861 — Editorial framing daraxonrasib (RMC-6236) and the broader RAS(ON) class as the inflection point in the KRAS-mutant PDAC story; pairs with the daraxonrasib Phase 1/2 primary publication featured above.
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Nature Communications — BCAT1 deficiency in TAMs raises intracellular crotonate, increases H3K14 crotonylation, upregulates lipid metabolism genes and drives an immunosuppressive phenotype; myeloid BCAT1 overexpression / adoptive transfer of BCAT1+ macrophages enhances anti-PD-1 response in HCC mouse models — a candidate TAM-directed adjuvant for IO.
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Gut — Multi-omics screen identifies AARS2 as the lactate-modifying enzyme catalyzing AP-2γ K444 lactylation, enabling TRIM28 binding, K63 ubiquitination and nuclear translocation; kukoamine A delivered via ZIF-8 nanocarriers reverses the axis and synergizes with PD-1 blockade in HCC.
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Nature Communications — ATRA induces retinoylation of ADAR1 → USP7 dissociation → ubiquitination and degradation; ATRA also induces PD-L1; ATRA + PD-1 reprograms TMEs from cold to hot in PDAC models. Mechanism-driven combination ready for clinical evaluation.
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Nature Communications — Pancreatic cancer–derived GDF15 expands CCN3+ Schwann cells via GFRAL, triggers AKT–RUNX2 → PFKM glycolytic reprogramming, enhances tumor innervation and pain sensitization; targeted GDF15–GFRAL inhibition alleviates PDAC pain in models. New target for one of pancreatic cancer's most refractory symptoms.
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