PubMed Trending Research Digest — October 25, 2026

Automated digest · 95 articles · 15 research areas · October 25, 2026

Overview

This week’s research highlights a strong push toward mechanism-driven precision medicine—especially in immunology and oncology. In IgA nephropathy, two complementary strategies targeting the complement axis (ravulizumab) and the B-cell survival pathway (povetacicept blocking BAFF/APRIL) both show early promise for reducing ongoing, proteinuric disease activity. In cancer, multiple studies dissect why therapies fail: stromal-immune signaling programs (e.g., SPP1+ macrophage WNT5A→MMP11 myCAF remodeling in lung adenocarcinoma), tumor-derived immunosuppressive circuits (DLL3high serotonin/TAM-mediated resistance to tarlatamab), and therapy-driven disruption of immune structures (neoadjuvant chemotherapy impairing tertiary lymphoid structures in EBV-associated gastric cancer). Together, these works frame resistance as a modifiable network rather than a static tumor trait.

A second dominant theme is the growing integration of advanced models and biomarkers to guide treatment selection. Long-read RNA sequencing uncovered STAT2 intron retention as a mechanistic determinant of checkpoint inhibitor response, while multiomic and machine-learning approaches map vulnerabilities in MSS colorectal cancer and define predictive immune product features for CAR T cell outcomes. Preclinical platforms are also expanding rapidly: new organoid systems (periosteal niches), improved imaging/segmentation pipelines (cochlear connectomics; spatial transcriptomics cell segmentation benchmarking), and engineered cellular tools (chemogenetic mitochondrial pyruvate delivery; in situ CAR-macrophage engineering for fibrotic liver). Finally, across several studies, metabolism and cell-death control emerge as actionable levers—ranging from ferroptosis vs apoptosis decisions in SCLC to lactate-driven metastatic dormancy in prostate cancer—suggesting that future combination regimens will increasingly pair immune modulation with metabolic and death-pathway targeting.

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Complement and immune-complex mechanisms in kidney disease

Characterization of IgA, IgA immune complexes and complement depositions in IgA nephropathy using laser microdissection and mass spectrometry.

This study examined IgA and complement deposition patterns in 22 human cases of IgA nephropathy using laser microdissection and mass spectrometry (LMD/MS). LMD/MS detected abundant IgA1 in 100% of cases and IgA2 in 82%, and identified the IgA J chain in 91% of cases, alongside characterization of complement deposits. These findings refine the molecular composition of IgA immune complexes and complement involvement in IgA nephropathy, supporting more targeted mechanistic and therapeutic strategies against complement-mediated glomerular injury.

Cara A, Singh RD, Berti GM et al. · Kidney international · (2026) · View on PubMed ↗

PARP1 directly disassembles nucleosomes to regulate DNA repair.

This mechanistic study investigated how poly(ADP-ribose) polymerase 1 (PARP1) regulates DNA repair by remodeling chromatin at DNA strand breaks in human cells. PARP1 was found to directly and asymmetrically evict histone dimers near breaks to generate oriented hexasomes, with HPF1 enabling stable PARylated hexasomes that promote recruitment of DNA- and PAR-dependent factors. The work is significant because it clarifies a direct PARP1 mechanism for overcoming the nucleosome barrier, informing how PARP-targeting therapies may influence DNA repair accessibility.

Verma A, Zhu C, Truong B et al. · Molecular cell · (2026) · View on PubMed ↗ · Free PDF ↗

Perforin triggers iron-induced mitochondrial damage to drive ferroptosis and anti-tumor immunity.

This study examined how perforin (Prf1) released by cytotoxic CD8+ T cells and NK cells affects tumor cell death pathways. Prf1 was shown to directly trigger iron- and lipid-dependent ferroptosis by inducing transferrin receptor endocytosis to increase iron uptake and by promoting endosomal–mitochondrial contacts that drive mitochondrial damage. The findings are important for anti-tumor immunity because they reveal a granzyme-independent Prf1 mechanism that could be leveraged to enhance ferroptosis-based tumor killing.

Bell HN, Nair K, Tison K et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

Taurine lowers inflammaging by regulating the NLRP3 inflammasome in macrophages.

This study assessed whether taurine influences aging-related inflammation by regulating the NLRP3 inflammasome in macrophages in both humans and mice. Aging increased circulating taurine, and experimentally elevating taurine in aged mice improved healthspan and reduced mortality from sepsis and inflammasome-mediated inflammation, while mechanistically showing that NLRP3 danger signals induce taurine efflux from macrophages as a proximal step to activate inflammasome and pyroptosis. These results suggest taurine as an enantiostatic, anti-inflammaging modulator that targets NLRP3-driven inflammatory cell death.

Guan C, Ryu S, Dong M et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

Cell-state-specific metabolic networks govern ferroptosis versus apoptosis in small cell lung cancer.

This study investigated how metabolic state determines whether small cell lung cancer (SCLC) cells undergo ferroptosis versus apoptosis, focusing on neuroendocrine (NE) versus non-NE cellular states. Integrated transcriptomic and metabolomic analyses identified a universal dependency on exogenous cysteine/cystine, where ASCL1-low cells underwent ferroptosis upon cystine depletion while ASCL1high cells underwent apoptosis and resisted ferroptosis. The findings are clinically relevant because they suggest state-specific metabolic vulnerabilities that could guide ferroptosis-targeting strategies in SCLC.

Kim JW, Bebber CM, Dai Y et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

Synoptic reporting of cytoreductive surgical procedures for patients with peritoneal malignancy based on the PSOGI-ESGO-ISSPP consensus.

This study developed a standardized synoptic reporting framework for cytoreductive surgery (CRS) for peritoneal malignancies (PM) by revising and operationalizing the PSOGI-ESGO-ISSPP consensus classification of peritonectomy and visceral resections among CRS surgeons. It produced a structured documentation format to capture the extent and complexity of peritoneal resection (aiming for CC-0 resection) to reduce variability in how procedures are described. Standardized CRS reporting should improve comparability across centers and strengthen research and outcome analyses in peritoneal oncology.

Bhatt A, Moran B, Fotopoulou C et al. · European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology · (2026) · View on PubMed ↗

Finerenone-Empagliflozin Combination Therapy in Apparent Resistant Hypertension: A CONFIDENCE Trial Post Hoc Analysis.

This post hoc analysis of the CONFIDENCE randomized trial evaluated whether finerenone plus empagliflozin lowers blood pressure in patients with chronic kidney disease and type 2 diabetes who have apparent treatment-resistant hypertension (aTRH). The analysis assessed whether aTRH status modifies the efficacy and safety of finerenone and empagliflozin using mixed models and related statistical methods. If consistent with the trial’s overall findings, the results could refine fourth-line/combination antihypertensive strategies for CKD patients with diabetes who are limited by hyperkalemia risk from spironolactone.

Agarwal R, Navaneethan SD, Correa-Rotter R et al. · JACC. Advances · (2026) · View on PubMed ↗ · Free PDF ↗

AGA/AASLD Clinical Practice Guideline on Management of Primary Biliary Cholangitis.

This AGA/AASLD clinical practice guideline synthesized evidence for diagnosing and managing primary biliary cholangitis (PBC) in patients across key clinical scenarios, including antimitochondrial antibody–negative disease and inadequate response to ursodeoxycholic acid (UDCA). It provides evidence-based recommendations for risk stratification, escalation of therapy after inadequate UDCA response, management of cholestatic pruritus, and prevention of recurrent disease after liver transplantation. The guideline is intended to standardize PBC care and improve outcomes by addressing major gaps in current clinical practice.

Levy C, Mayo MJ, Carey EJ et al. · Gastroenterology · (2026) · View on PubMed ↗

Efficacy and Safety of Guselkumab in Patients with Crohn’s Disease and Ulcerative Colitis: A Prospective Real-World Study.

This prospective real-world study enrolled adults with inflammatory bowel disease (Crohn’s disease and ulcerative colitis) initiating guselkumab (an IL-23p19 inhibitor) at a tertiary center and followed them for up to 52 weeks. It evaluated clinical remission using HBI <5 for Crohn’s disease and SCCAI ≤2 for ulcerative colitis, alongside biochemical measures and adverse events. The findings provide practical effectiveness and safety evidence for guselkumab outside randomized trials, supporting treatment decisions in routine IBD care.

Shafrir A, Choi D, Capucci LC et al. · Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · (2026) · View on PubMed ↗

Psoriasis: Which therapy for which patient, updated, part II. Focus on special populations and chronic infections.

This updated clinical review addressed how to select systemic therapy for different patient subgroups with moderate-to-severe psoriasis, focusing on special populations and chronic infections. It summarizes evidence and practical considerations for therapies in settings such as pregnancy, pediatric patients, hepatitis, HIV, latent tuberculosis, and difficult-to-treat phenotypes. The update helps clinicians match psoriasis treatments to comorbid infection risk and population-specific evidence gaps.

Karpoff K, Pasumarthi A, Lebwohl M · Journal of the American Academy of Dermatology · (2026) · View on PubMed ↗

Conspecific-Associated Ultrasonic Vocalizations Modulate Resource-Directed Exploratory Behavior in Rats.

This rat study tested whether conspecific-associated ultrasonic vocalizations (USVs) modulate resource-directed exploratory behavior across a physical barrier using a sucrose–capsaicin dual-choice paradigm. It quantified drinking bout counts, zone occupancy, locomotor trajectories, and USV characteristics, then used USV playback and broadband white-noise masking to assess causal contributions of acoustic cues. The results clarify how social acoustic signals can bias motivated exploration, informing neural mechanisms of social influence on decision-making.

Huang Y, Luo H, Xie B et al. · Behavioural brain research · (2026) · View on PubMed ↗

Single-cell landscape of alcohol-related hepatitis reveals serum amyloid a hepatocytes as key drivers of disease pathogenesis.

The study used single-cell RNA sequencing on liver biopsies from patients with alcohol-related hepatitis (AH), early-stage alcohol-related liver disease (ALD), and healthy individuals, and validated markers by immunofluorescence, then used liver biopsy-derived organoids exposed to AH-conditioned medium to test disease-relevant mechanisms. The key finding was that serum amyloid A (SAA)–expressing hepatocytes emerge as key drivers of AH pathogenesis, with organoid experiments supporting their functional contribution under AH-like conditions. This identifies SAA hepatocyte subpopulations as mechanistic targets in AH, linking cellular heterogeneity to disease-driving inflammatory programs.

Martínez-Álvarez A, Rill-Hinarejos A, Gratacós-Ginès J et al. · Hepatology (Baltimore, Md.) · (2026) · View on PubMed ↗ · Free PDF ↗

Ravulizumab in IgA Nephropathy - Interim Analysis of a Phase 3 Trial.

This phase 3 randomized trial studied ravulizumab, a terminal complement inhibitor, in adults with biopsy/clinical IgA nephropathy and persistent proteinuria despite standard therapy. Interim results showed that ravulizumab reduced complement-mediated disease activity compared with control, with effects assessed on renal outcomes such as proteinuria and kidney function. These findings support C5-targeted complement blockade as a potential disease-modifying therapy for IgA nephropathy in patients with ongoing proteinuric disease.

Barratt J, Farag YMK, Rice K et al. · The New England journal of medicine · (2026) · View on PubMed ↗

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B-cell / BAFF-APRIL pathway targeted therapies in IgA nephropathy

Interim Analysis of a Phase 3 Trial of Povetacicept in IgA Nephropathy.

This ongoing phase 3 double-blind, placebo-controlled trial evaluated povetacicept (a TACI-Fc fusion engineered to inhibit both BAFF and APRIL) in participants with biopsy-proven IgA nephropathy receiving stable background therapy. Interim data indicated that dual BAFF/APRIL inhibition with povetacicept produced clinically meaningful improvements in IgA nephropathy outcomes versus placebo. If confirmed in final analyses, povetacicept could represent a targeted B-cell–pathway therapy for IgA nephropathy beyond standard-of-care.

Barratt J, Zhang H, Han SH et al. · The New England journal of medicine · (2026) · View on PubMed ↗

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Cancer immunotherapy resistance and tumor microenvironment (TME)

SPP1⁺ macrophage-derived WNT5A contributes to MMP11⁺ myCAF-mediated matrix remodeling and immunotherapy resistance in lung adenocarcinoma.

This Journal of Translational Medicine study investigated lung adenocarcinoma stromal-immune interactions by focusing on SPP1+ macrophage-derived WNT5A and its role in driving MMP11+ myCAF-mediated matrix remodeling and resistance to PD-1 blockade. Using integrated bulk transcriptomics, single-cell RNA sequencing, and spatial transcriptomics with clinical immunotherapy cohorts, the authors identified high-risk cell subpopulations and characterized cell-cell communication programs linked to immunotherapy resistance. The findings are significant because they implicate a specific macrophage–CAF signaling axis (WNT5A–MMP11) as a mechanistic driver and potential therapeutic target to overcome PD-1 resistance in LUAD.

Wang M, Zhang P, Li X et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Single‑cell multi‑omics analysis reveals TGF-β1-RUNX2-mediated matCAF differentiation and its role in remodeling the lymph node metastatic microenvironment in bladder cancer.

The study used integrated single-cell RNA sequencing, spatial transcriptomics, clinical cohorts, and functional models to define lymph node metastasis (LNM)-associated matrix-remodeling cancer-associated fibroblast (matCAF) differentiation in bladder cancer. It found that hybrid CCND1+ malignant epithelial cells drive matCAF differentiation via FOS-dependent TGFB1 transcription and TGF-β signaling, producing an LNM-enriched matCAF state marked by LRRC15 and POSTN that predicts worse survival and reduced immunotherapy response. This mechanistic stromal map identifies a TGF-β1–RUNX2-linked pathway as a potential therapeutic target to improve outcomes in bladder cancer patients with lymph node metastases.

He W, Chen Q, Wang Z et al. · Oncogene · (2026) · View on PubMed ↗

Neoadjuvant chemotherapy interferes with tertiary lymphoid structure formation in Epstein-Barr virus-associated gastric cancer.

The study assessed how neoadjuvant chemotherapy affects tertiary lymphoid structure (TLS) formation in Epstein-Barr virus-associated gastric cancer (EBVaGC) using a large locally advanced cohort plus spatial transcriptomics and single-cell atlases. It found that EBVaGC has enhanced TLS formation compared with EBV-negative gastric cancer and that invasive-margin TLS (IM-TLS) predicts favorable prognosis, but neoadjuvant chemotherapy disrupts TLS formation and shows limited efficacy in EBVaGC. It also reported that recurrent tumors show increased neutrophil infiltration around TLS, suggesting therapy-associated immune remodeling that may blunt TLS-driven anti-tumor immunity.

Bi J, Hu S, Sun Y et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Impact of extramedullary plasmacytoma on outcomes in patients with relapsed refractory multiple myeloma treated with talquetamab: U.S. Myeloma Immunotherapy Consortium.

The study evaluated how extramedullary plasmacytoma (EMD) affects outcomes in relapsed/refractory multiple myeloma treated with talquetamab by analyzing real-world data from 360 U.S. patients across 15 centers. It found similar overall response rates across EMD categories—68% in soft tissue plasmacytoma (STP) classified as EMD, 63% in paraskeletal disease (PSD), and 65% in No-STP—with no significant differences (p=0.8). This indicates that, in talquetamab-treated patients, the presence and anatomical classification of extramedullary disease may not strongly predict initial response, guiding risk stratification in clinical practice.

Afrough A, Pasvolsky O, Portuguese AJ et al. · Blood cancer journal · (2026) · View on PubMed ↗ · Free PDF ↗

Lung neuroendocrine cancer induces immunosuppressive macrophages via serotonin to drive resistance to the T cell engager tarlatamab.

This study investigated how lung neuroendocrine cancers develop resistance to the DLL3×CD3 T cell engager tarlatamab by inducing immunosuppressive tumor-associated macrophages (TAMs). It showed that serotonin (5-HT) produced by DLL3high neuroendocrine cancers via TPH1 upregulation drives TAM-mediated impairment of CD8+ T cell function and promotes tarlatamab resistance. These findings suggest that targeting the DLL3high–TPH1/serotonin–TAM axis could improve responses to tarlatamab in small cell lung cancer.

Nomura K, Fukami T, Kato S et al. · Cancer cell · (2026) · View on PubMed ↗

Lifestyle-induced regulatory T cell fragility primes adverse events after immune checkpoint blockade.

The study developed and tested the lifestyle-induced susceptibility to irAEs (LISA) preclinical model to model diet-driven susceptibility to anti–PD-1 immune checkpoint blockade toxicity in vivo. LISA recapitulated multi-organ immune-related adverse events with immune infiltration and cytokine production, with severity depending on sex, age, treatment modality, and immunotherapy response, and implicated Akkermansia muciniphila–associated dysbiosis in aberrant immune activation. This provides a mechanistic, human-like platform to predict and dissect drivers of immune checkpoint inhibitor toxicity and to guide risk stratification or microbiome-targeted interventions.

Patra D, Wolfgang K, Ye C et al. · Cell · (2026) · View on PubMed ↗

ILC2-derived IL-9 promotes eosinophil-mediated antitumor activity.

The study investigated how group 2 innate lymphoid cells (ILC2s) control tumor immunity by combining human sequencing analyses with genetic ablation mouse models and adoptive transfer experiments. It found that GITR engagement on tumor-infiltrating ILC2s induces ATF3-dependent, robust IL-9 production, and that ILC2-derived IL-9 promotes eosinophil survival, tissue retention, and cytotoxicity by increasing tumor IL-9 receptor expression. This is significant because it links a defined ILC2 signaling axis (GITR→ATF3→IL-9) to eosinophil-mediated antitumor activity, suggesting actionable immunotherapy strategies.

Ko YG, Ham J, Koh J et al. · Science immunology · (2026) · View on PubMed ↗

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Checkpoint blockade and next-generation immunotherapy trials

COMPANION-002: A Randomized Phase 2/3 Trial of Tovecimig Plus Paclitaxel versus Paclitaxel Alone as a Second-line Therapy in Patients with Advanced Biliary Tract Cancer.

COMPANION-002 studied tovecimig, a bispecific antibody targeting delta-like ligand-4 (DLL4) and VEGF-A, combined with paclitaxel versus paclitaxel alone as second-line therapy in patients with advanced biliary tract cancer who had received one prior systemic therapy. The key efficacy endpoint was RECIST v1.1 objective response rate assessed by blinded independent central review (BICR), with treatment given as paclitaxel 80 mg/m2 on days 1, 8, and 15 plus tovecimig 10 mg/kg on days 1 and 15. If positive, this strategy could expand targeted options for pretreated advanced BTC by improving response outcomes beyond paclitaxel alone.

Azad NS, Hu I, Pathak P et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Bispecific dual T cell agonist invikafusp alfa in solid tumors: the phase 1/2 START-001 trial.

This phase 1/2 START-001 trial studied invikafusp alfa (invika), a bispecific dual T cell agonist antibody targeting Vβ6/Vβ10 T cell subsets, in participants with mostly immune checkpoint blockade (ICB)-resistant, antigen-rich solid tumors. The phase 1 portion completed dose escalation (n=34) without reaching the maximum tolerated dose, and phase 2 initially enrolled 18 participants to evaluate anti-tumor activity at the recommended phase 2 dose. The study is significant because it tests a Vβ-subset–directed T cell activation strategy as a potential next-generation immunotherapy for ICB-resistant solid tumors.

Sullivan RJ, Tschernia NP, Friedman CF et al. · Nature medicine · (2026) · View on PubMed ↗

Perioperative pembrolizumab or placebo plus neoadjuvant cisplatin and gemcitabine in participants with muscle-invasive bladder cancer who are eligible for cisplatin: the double-blind, phase III KEYNOTE-866 study.

The KEYNOTE-866 double-blind phase III trial studied perioperative pembrolizumab versus placebo added to neoadjuvant cisplatin plus gemcitabine and followed by radical cystectomy with pelvic lymph node dissection in cisplatin-eligible muscle-invasive bladder cancer (MIBC). The key finding is the evaluation of whether adding the PD-(L)1 inhibitor pembrolizumab improves perioperative outcomes compared with placebo in this cisplatin-eligible population (primary/secondary results are truncated). This is significant because it tests whether perioperative immune checkpoint blockade can improve cure-relevant endpoints in MIBC treated with standard cisplatin-based chemotherapy and surgery.

Bedke J, Arkosy P, Nishiyama H et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗

Neoadjuvant nivolumab plus gemcitabine-cisplatin followed by postsurgical adjuvant nivolumab versus neoadjuvant gemcitabine-cisplatin in patients with muscle-invasive bladder cancer: final results from the phase III CA017-078 trial.

The phase III CA017-078 (ENERGIZE) trial investigated neoadjuvant nivolumab plus gemcitabine-cisplatin followed by adjuvant nivolumab versus neoadjuvant gemcitabine-cisplatin alone in previously untreated resectable muscle-invasive bladder cancer eligible for radical cystectomy. The key finding is that the study evaluated co-primary endpoints including pathological complete response (ypT0N0) and event-free survival, with results reported as final in the abstract (numerical outcomes are truncated). Scientifically and clinically, it clarifies whether adding PD-1 blockade to perioperative chemotherapy improves pathologic response and longer-term outcomes in MIBC.

Sonpavde G, van der Heijden MS, Gupta S et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Nivolumab plus relatlimab with platinum-doublet chemotherapy versus nivolumab with platinum-doublet chemotherapy in stage IV or recurrent non-small cell lung cancer: clinical, translational, and patient-reported outcomes results from the phase II RELATIVITY-104 study.

The RELATIVITY-104 phase II study (Part 2) compared first-line nivolumab plus relatlimab with platinum-doublet chemotherapy versus nivolumab with platinum-doublet chemotherapy in patients with stage IV or recurrent non-small cell lung cancer (NSCLC). The key finding is that this head-to-head design evaluated objective response rate (ORR) as the primary endpoint for the dual checkpoint approach (PD-1 plus LAG-3 blockade) in NSCLC (full results are truncated). This is significant because it tests whether adding LAG-3 inhibition to PD-1 blockade improves response and patient-reported outcomes beyond PD-1 plus chemotherapy alone.

Girard N, Burotto M, Paz-Ares LG et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗

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Targeted oncology (RAS/MAPK, KRAS, AKT, CDK4/6, etc.) and resistance

Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic cancer: the randomized phase 2 AMPLIFY-7P trial.

This randomized phase 2 AMPLIFY-7P trial studied lymph node-targeted, mKRAS-specific amphiphile vaccination with camupepimut (ELI-002 7P) in stage I–III KRAS-mutated pancreatic adenocarcinoma patients without recurrence after 6 months of standard therapy. The primary endpoint of disease-free survival (DFS) was not met (median 23.8 vs 21.2 months; HR 0.85, P=0.5329), though prespecified/exploratory analyses suggested informative trends. Scientifically and clinically, the trial clarifies the benefit-risk profile of ELI-002 7P and guides future biomarker-driven optimization of KRAS-targeted T cell vaccination in PDAC.

George B, Singh H, Devoe CE et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Oncogenic RAS as an adaptive signaling ecosystem: context-dependent vulnerabilities and resistance-informed therapeutic design.

This review analyzed oncogenic RAS signaling as an adaptive ecosystem, focusing on context-dependent vulnerabilities and how resistance informs therapeutic design across RAS-driven cancers. It highlights that direct RAS targeting (including KRAS G12C inhibitors and KRAS G12C–EGFR combinations) and newer agents such as the multiselective RAS(ON) inhibitor daraxonrasib (FDA-approved for metastatic pancreatic adenocarcinoma) show lineage- and allele-specific differences in durability, and it discusses investigational approaches like the KRAS G12D degrader setidegrasib. The significance lies in reframing RAS therapy selection and combination strategies around adaptive signaling and resistance mechanisms rather than target engagement alone.

Hamidi AA, Moaven O, Mahmoudian RA et al. · Experimental hematology & oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Early WEE1 inhibition prevents senescence-like epigenetic reprogramming of pioneer TMZ-resistant cells and synergizes with temozolomide in MYC-high glioblastoma.

This study examined how early WEE1 inhibition affects senescence-like epigenetic reprogramming in patient-derived temozolomide (TMZ)-resistant glioblastoma pioneer resistant (P-R) cells, particularly in MYC-high glioblastoma models. The key finding is that early WEE1 inhibition prevents the senescence-like epigenetic reprogramming of TMZ-resistant P-R cells and synergizes with TMZ in MYC-high glioblastoma. This is significant because it identifies WEE1 as a mechanistic vulnerability to block early survival/resistance programs and improve TMZ efficacy in a defined molecular subgroup (MYC-high).

Wu Y, Chang Y, Qin X et al. · Cancer letters · (2026) · View on PubMed ↗

Capivasertib plus abiraterone in PTEN-deficient de novo metastatic hormone-sensitive prostate cancer: updated survival analysis from CAPItello-281.

The CAPItello-281 phase III study updated survival analyses for capivasertib plus abiraterone versus placebo plus abiraterone in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC). The key finding is that capivasertib plus abiraterone previously improved radiographic progression-free survival (rPFS; HR 0.81, 95% CI 0.66–0.98) and the interim overall survival (OS) analysis showed no clear OS advantage yet (HR 0.90, 95% CI 0.71–1.15 at 26% maturity). This is clinically important because it refines expectations for survival benefit in a biomarker-defined population (PTEN-deficient) while supporting continued evaluation of AKT-pathway inhibition strategies.

Fizazi K, Clarke NW, De Santis M et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Overall survival with adjuvant ribociclib plus nonsteroidal aromatase inhibitor in patients with high-risk HR+/HER2- early breast cancer: Six-year follow-up of the NATALEE trial.

The NATALEE trial reported 6-year overall survival follow-up for ribociclib plus a nonsteroidal aromatase inhibitor (NSAI) versus NSAI alone in adults with high-risk HR+/HER2- early breast cancer. The key finding is the prespecified long-term efficacy and safety assessment of ribociclib-containing therapy after an earlier invasive disease-free survival benefit (details of the OS magnitude are truncated in the abstract). Clinically, extended follow-up is crucial to determine whether the CDK4/6 inhibitor strategy translates into durable overall survival gains in this high-risk early breast cancer group.

Slamon DJ, Hortobagyi GN, Stroyakovskiy D et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Dynamic force sensing by bone delays aging and extends lifespan.

This preclinical study tested whether impaired bone mechanosensing accelerates aging and whether dynamic tibial axial loading can extend lifespan in mice, using osteocyte-specific deletion of the mechanosensory channel Piezo1. Reduced Piezo1-dependent mechanosensing in osteocytes accelerated whole-body aging, while dynamic tibial axial loading (DTAL) at 20–24 months extended healthspan and lifespan and reversed bone marrow immunosenescence. These results support a mechanistic link between Piezo1-mediated bone force sensing and systemic aging, suggesting mechanical interventions or mechanosensing pathways as potential anti-aging targets.

Zhang Z, Cai Z, Liu S et al. · Cell metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

Multiomic characterization of microsatellite-stable colorectal cancer reveals distinct biology and targetable vulnerabilities.

This multiomic study analyzed microsatellite-stable (MSS) colorectal cancer using integrated machine-learning and multiomic-phenomic frameworks (including iPhenMap) across ~2,000 tumor samples with ~4,500 molecular profiles and ~195,246 single cells/nuclei. It revealed distinct biological programs and targetable vulnerabilities, including replication stress, right-sided biology, glutaminolysis-driven metabolic reprogramming, and MYC–E2F transcriptional networks linked to epigenetic remodeling. The results provide a roadmap for precision targeting in MSS CRC, a subtype that has historically lacked effective targeted therapies.

Sadanandam A, O’Farrell AC, Miller IS et al. · Cancer cell · (2026) · View on PubMed ↗ · Free PDF ↗

Low-grade serous ovarian cancer: 2026 expert consensus report.

This 2026 expert consensus report synthesized emerging evidence to update clinical recommendations for low-grade serous ovarian cancer (LGSOC), a rare epithelial malignancy with frequent MAPK pathway alterations and hormone receptor expression. The consensus provides updated guidance across pathology and molecular testing, and frontline and recurrent treatment strategies in newly diagnosed and relapsed disease. This is significant because it standardizes care for a biologically distinct, treatment-resistant cancer with a prolonged relapsing course.

Grisham RN, Slomovitz B, Podder V et al. · Gynecologic oncology · (2026) · View on PubMed ↗ · Free PDF ↗

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Cancer cell death mechanisms (ferroptosis, ferroptosis vs apoptosis, non-apoptotic death)

BAK and BAX form a multiprotein complex to drive mtDNA efflux and caspase-independent cell death.

This study examined the mechanism of mitochondrial DNA (mtDNA) efflux and caspase-independent cell death by analyzing how BAK and BAX form a multiprotein complex. The authors purified a complex containing BAK, BAX, BH3-only activators, VDAC1/VDAC2, and prohibitins, and showed that BAX-BAK activation drives VDAC closure, mitochondrial calcium influx, and mtDNA efflux. By defining the BAK/BAX–VDAC/prohibitin machinery that governs mtDNA release, the work clarifies a non-apoptotic death pathway with potential therapeutic relevance.

Yang S, Kim H, Liao G et al. · Science (New York, N.Y.) · (2026) · 1 citations · View on PubMed ↗

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Tumor metabolism and metabolic reprogramming

Chemogenetic activation of mitochondria counteracts the Warburg effect in tumor cells.

This study created a chemogenetic mitochondrial activation tool, Grubraw, that generates pyruvate from D-alanine directly in the mitochondrial matrix to bypass restricted pyruvate influx and test effects on tumor metabolism. It reports that Grubraw-produced mitochondrial pyruvate increases oxidative metabolism in cancer cells and counteracts the Warburg effect. The significance is that chemogenetic control of mitochondrial pyruvate flux provides a mechanistic strategy to disrupt tumor metabolic reprogramming.

Bass DY, Potekhina ES, Ivanenko AV et al. · Nature chemical biology · (2026) · 1 citations · View on PubMed ↗

MCT6 is an intestinal Lac-Phe exporter required for metformin-associated weight loss.

The study investigated how the intestinal transporter MCT6/SLC16A5 regulates systemic activity of the anorexigenic metabolite N-lactoyl-phenylalanine (Lac-Phe), including during metformin treatment and high-intensity exercise, using in vitro transport assays and in vivo measurements. MCT6 was identified as a physiologic Lac-Phe exporter that mediates Lac-Phe efflux, maintains normal circulating Lac-Phe levels, and is required for metformin-associated weight loss. These findings link a specific intestinal gene (SLC16A5/MCT6) to a defined metabolite (Lac-Phe) and provide a mechanistic explanation for how metformin can drive organism-wide metabolic effects.

Xiao S, Tung AS, Spaas J et al. · Cell · (2026) · View on PubMed ↗ · Free PDF ↗

Primary tumor-derived lactate primes prostate cancer cells for a dormant fate.

The study investigated how lactic acid (LA) from the primary prostate tumor microenvironment influences disseminated cancer cell fate, focusing on LA-uploading prostate cancer cells and the nuclear receptor COUP-TF1/NR2F1. It found that LA primes prostate cancer cells for a dormant state characterized by proliferation delay and increased stemness, therapy tolerance, and invasiveness, mediated by COUP-TF1/NR2F1 activation and LA-driven lipid droplet accumulation. This is significant because it identifies a specific metabolic cue and transcriptional pathway that may govern metastatic dormancy, offering potential targets to prevent relapse.

Ippolito L, Pranzini E, Gangarossa G et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

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Organoids, models, and advanced experimental platforms (organoids, CAR-M, CAR T, imaging, segmentation)

CochleaNet: deep learning-based image analysis for cochlear connectomics and gene therapy.

CochleaNet studied a deep learning framework for cochlear connectomics and gene-therapy–relevant analysis using volumetric light-sheet microscopy of decalcified, cleared, fluorescently labeled cochleae. The method reconstructs cochlear anatomy and performs segmentation of inner hair cells, spiral ganglion neurons, and afferent synapses, including tonotopy and fluorescent expression pattern analysis, and was validated against manual image analysis. This is significant because it can accelerate quantitative, scalable mapping of cochlear cellular connectivity and gene-expression readouts needed for evaluating gene and optogenetic therapies for deafness.

Roos L, Diniz AM, Koert E et al. · Molecular therapy : the journal of the American Society of Gene Therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Benchmarking segmentation methods for spatial transcriptomics.

This benchmarking study evaluated 11 cell segmentation methods for spatial transcriptomics across 15 datasets from 5 spatial transcriptomics technologies and 12 human and mouse tissue types. It finds that segmentation performance varies substantially by platform and biological context and proposes biologically informed evaluation metrics to quantify segmentation quality, transcript recovery, and cell composition. Scientifically, the work provides a standardized way to choose and validate segmentation pipelines, improving downstream cell identity assignment and spatial interpretation.

Martínez-de-Morentin X, Khan SA, Maillo A et al. · Nature methods · (2026) · View on PubMed ↗ · Free PDF ↗

Long-Term Expandable Periosteal Organoids Reconstruct a Functional Regenerative Niche That Support Hematopoietic Stem Cell Maintenance and Bone Repair.

This study developed a long-term expandable periosteal organoid system from periosteum to model skeletal regenerative niches and tested its ability to support hematopoietic stem cell (HSC) maintenance and bone repair. It reports that the organoids can be propagated for >20 passages while preserving cellular heterogeneity, multilineage differentiation potential, and genomic integrity, with single-cell transcriptomics showing sustained periosteal lineages and regenerative signaling programs. This is significant because it provides a stable in vitro platform to study periosteum biology and to support translational research for HSC maintenance and bone regeneration.

Qing J, Gu L, Fu L et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Ghost Neuron preparation unlocks high-resolution structural mapping of intracellular architecture in axons.

The study introduced the “Ghost Neuron” preparation to enable high-resolution structural mapping of intracellular architecture in axons using cellular cryo-electron microscopy (cryo-EM). It found that brief hypotonic treatment followed by controlled mechanical rupture immediately before freezing removes the plasma membrane and reduces cytoplasmic density, improving contrast while preserving neurite topology for ultrastructural analysis. This technique expands cryo-EM’s ability to resolve molecular structures in narrow neuronal projections where dense cytoplasm previously limited imaging.

Bodakuntla S, Marelli J, Vasquez-Montes V et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Creating the first synthetic plastid genome in plants.

This article describes efforts to create the first synthetic plastid genome in plants, focusing on genome writing/engineering of the compact plastid (chloroplast) genome rather than sequencing. The key finding is the demonstration of feasibility for synthetic plastid genome construction as a scalable “genome writing” target in plants. This is scientifically significant because it opens a practical route to programmable, high-throughput chloroplast engineering for plant biotechnology.

Lenaghan SC, Bock R, Dunkelmann DL et al. · Trends in plant science · (2026) · View on PubMed ↗

Programmable Recognition of Organyl 5’-Phosphates by Human Argonaute-2.

This chemical-biology study investigated how human Argonaute-2 (AGO2) recognizes and loads small RNA guide strands bearing diverse 5’-phosphate (5’-P) chemical modifications. AGO2 was shown to accommodate a substantially broader range of 5’-P derivatives than previously recognized, and specific 5’-P mimics can engage novel protein interactions that distinguish AGO2 recognition from competing degradation pathways. These results are significant for designing chemically modified siRNA drugs that retain AGO2 loading while improving stability against 5’-P–dependent enzymatic degradation.

Carrigan-Broda T, Gebert LFR, Hildebrand S et al. · Journal of the American Chemical Society · (2026) · View on PubMed ↗

Outcomes of CD20-targeting CAR T-cell therapy in patients with advanced melanoma: MB-CART20.1 Melanoma phase I trial.

This phase I, prospective, open-label 3+3 trial evaluated autologous anti-CD20 CAR T cells (MB-CART20.1) in patients with advanced melanoma refractory to approved therapies, after lymphodepleting chemotherapy and a single CAR T infusion. The study’s key findings focused on safety/tolerability and preliminary anti-tumor activity of CD20-targeting CAR T therapy in this population. Scientifically and clinically, it tests whether CD20+ tumor microenvironment targets (including putative cancer stem cell populations) can be exploited in melanoma using a defined CAR T construct.

Balke-Want H, Theurich S, Gödel P et al. · European journal of cancer (Oxford, England : 1990) · (2026) · View on PubMed ↗

In situ CAR-M engineered by liposomal mRNA nanomedicine remodels fibrotic microenvironment for ameliorating liver fibrosis.

The study developed an in situ chimeric antigen receptor macrophage (CAR-M) engineering approach in which a phosphatidylserine (PS)-incorporated, macrophage-targeted lipid nanoparticle (LNP) delivers CAR messenger RNA (mRNA) and Cas9 mRNA to remodel the fibrotic liver microenvironment. The key finding was that PS-LNP–mediated in situ CAR-M engineering remodels fibrotic microenvironmental cues and ameliorates liver fibrosis without requiring complex ex vivo CAR-M preparation. This provides a clinically more translatable strategy for generating gene-edited, antigen-specific macrophages using LNP-delivered CAR mRNA and Cas9 mRNA to treat chronic liver fibrosis.

Xiao H, Li X, Cai K et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Gastric Mixed Neuroendocrine-Non-neuroendocrine Neoplasms Develop from POU2F3+ Multipotent Progenitors.

This study investigated the cellular origin of gastric mixed neuroendocrine–non-neuroendocrine neoplasms (MiNENs) by identifying a POU2F3+ epithelial population and mapping its differentiation using lineage tracing and single-cell RNA sequencing. The authors found that POU2F3+ cells comprise distinct progenitor and lineage-committed subpopulations (including SOX2+SOX9+ progenitors and POU2F3+DCLK1+ tuft-like cells) that diverge toward the dual MiNEN lineages. These results implicate POU2F3+ multipotent progenitors as a driver of gastric MiNEN heterogeneity, providing a mechanistic framework for future targeted therapies.

Lin M, Chen Q, Lin GT et al. · Cancer research · (2026) · View on PubMed ↗ · Free PDF ↗

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Epigenetics, chromatin, and transcriptional regulation

XIST drives X-chromosome inactivation and safeguards female extraembryonic cells in humans.

The study investigated how XIST regulates X-chromosome inactivation (XCI) during human extraembryonic differentiation by differentiating naive human pluripotent stem cells into trophoblast stem cells and extraembryonic mesoderm cells. It found that extraembryonic differentiation is temporally linked to XCI, with an atypical inactive-X chromatin state lacking DNA methylation and canonical heterochromatin marks, and that loss of function of XIST prevents XCI establishment in humans. This clarifies a human-specific requirement for XIST in safeguarding extraembryonic cell development.

Panda A, Carrillo L, Balaton BP et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Retroviral insertions contributed to the divergence of human and chimpanzee brains.

This study examined whether lineage-specific endogenous retrovirus insertions (chimpanzee PTERV1, absent in humans) contributed to human–chimpanzee brain divergence by analyzing epigenomic regulation in chimpanzee neural organoids. It found that PTERV1 insertions are heavily DNA methylated and form over 150 species-specific heterochromatin domains with potential to alter gene regulation. The significance lies in providing a mechanistic route—retroviral epigenetic remodeling—by which noncoding regulatory elements could influence brain evolution.

Gerdes P, Karlsson O, Garza R et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Loss of KAT5-dependent H2A.Z acetylation provokes chromosomal instability in recurrent pregnancy loss.

The study investigated how trophoblast-specific loss of the acetyltransferase KAT5 (Kat5) and acetylation-defective mutants (including H2A.Z acetylation–blocking H2az1-K5R K8R K12R K14R) affect chromosomal stability during mouse trophoblast cell division in recurrent pregnancy loss. The key finding was that KAT5 depletion or preventing H2A.Z acetylation provokes severe chromosomal instability (CIN), causing embryonic lethality, with mechanistic support from integrated RNA-seq and CUT&Tag in mouse trophoblast stem cells. These results link the KAT5–H2A.Z acetylation axis to trophoblast genome stability, identifying a potential epigenetic vulnerability underlying recurrent pregnancy loss.

Bi S, Chen Y, Zhang L et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Histone methyltransferase NSD2 shapes CD8+ T cell fates through the H3K36me2-Zbtb20 axis.

The study examined how the histone methyltransferase NSD2 regulates CD8+ T cell differentiation during acute viral infection via an H3K36me2–Zbtb20 epigenetic axis. The key finding was that NSD2 deficiency enhances early expansion of activated CD8+ T cells but severely impairs survival fitness during the contraction phase, leading to a disproportionate collapse of the CD8+ T cell response. This establishes NSD2-dependent H3K36me2–Zbtb20 signaling as a critical determinant of CD8+ T cell fate and persistence, with implications for improving antiviral and immunotherapeutic strategies.

Yuan S, Xu Y, Liu H et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

Structural basis for start codon selection by eIF5-mimic proteins.

The study determined the structural and biochemical basis for how eIF5-mimic proteins (5MPs; 5MP1/BZW2 and 5MP2/BZW2) control start codon selection and restrict non-AUG initiation, including for oncogenic c-Myc mRNAs with alternative start sites. The key finding was that cryo-EM structures of 48S preinitiation complexes show 5MP1 bound at the A site of the small ribosomal subunit, stabilizing an open PIC conformation and thereby repressing translation depending on start-codon sequence context. This advances the mechanistic understanding of translational control by 5MPs, with potential relevance to diseases where altered start codon usage drives aberrant proteoform expression.

Zottig X, Huang CY, Seraj Z et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

A noncanonical meiotic cohesin complex associates with specific MCM complexes to promote cohesion establishment and homolog bias.

The study investigated meiosis-specific cohesion in Drosophila by characterizing a noncanonical meiotic cohesin complex (including the SOLO subunit) and its interactions with specific MCM complexes. The key finding was that SOLO directly interacts with SUNN, SSEP, and SMC1 and also binds MCM4 and MCM6 (and MMS22L) to promote cohesion establishment and homolog bias, with conserved interactions across Drosophila melanogaster and Zeugodacus cucurbitae. This reveals a conserved mechanism linking a specialized cohesin complex to MCM replication machinery to ensure accurate homolog segregation during meiosis.

Ma L, Jin Q, Hu D et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

TET2-driven activation of AGO2 links epigenetic remodeling to myeloid commitment and leukemia.

The study defined how the DNA dioxygenase TET2 regulates human myeloid commitment and leukemia by integrating DNA methylation, chromatin accessibility, 3D genome architecture, transcriptional profiling, and TET2 chromatin occupancy. The key finding was that TET2-bound regulatory regions gain short- and long-range chromatin interactions and that a subset of distal enhancer-enriched sites undergoes TET2-driven demethylation and activation, with functionally validated downstream targets linking TET2 activity to lineage programs. This mechanistically connects TET2-driven epigenetic remodeling to AGO2 activation and myeloid differentiation, offering insight into how TET2 mutations promote leukemogenesis.

Lazarenkov A, Valcárcel G, Martinez A et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

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Biomarkers and diagnostic/prognostic prediction (including AI/ML biomarkers)

GClnc1 as an emerging oncogenic regulator with mechanistic insights and clinical implications in human cancers.

This iScience review examined gastric cancer-related long non-coding RNA1 (GClnc1) across human cancers, focusing on mechanistic regulation of pathways including p53, MYC, NF-κB, and the SIRT3/SOD2 axis. It reports that GClnc1 promotes proliferation, inhibits apoptosis, and enhances drug resistance and metastasis, with aberrant tissue expression and altered circulating/exosomal levels (including exosomal GClnc1) proposed for diagnostic/prognostic use and fluorouracil response prediction. These findings support GClnc1 as a potential multi-cancer biomarker and therapeutic target, particularly for early gastric cancer detection and treatment stratification.

Dong Q, He Y, Yu R et al. · iScience · (2026) · View on PubMed ↗ · Free PDF ↗

Genetic prioritization of HSDL2 in suicide and intentional self-harm: multi-omics evidence linking lipid metabolism and neuronal vulnerability.

This BMC Medicine study prioritized genetically supported biological targets for suicide and intentional self-harm (SSH) and highlighted HSDL2 as a candidate, using multi-omics evidence. It integrated transcriptomic and proteomic Mendelian randomization, colocalization, and sensitivity diagnostics with SSH outcomes from FinnGen R12 (11,538 cases and 488,810 controls), and used eQTLGen/GTEx plus UKB-PPP/ARIC for transcriptomic and proteomic analyses. The work is significant because it provides a gene-level, genetically informed route to identify lipid metabolism–linked neuronal vulnerability mechanisms that could guide future SSH risk biology and target development.

Zhang Z, Wu Y, Meng F et al. · BMC medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Mitochondrial dysfunction in neurology: biomarkers and clinical implications.

This Nature Reviews Neurology article reviewed mitochondrial dysfunction across neurological disorders and focused on mitochondrial biomarkers for clinical translation. It describes how biomarkers of impaired oxidative phosphorylation and related mitochondrial processes could improve diagnostic accuracy, patient stratification, monitoring of disease progression, and therapeutic response, using primary mitochondrial diseases as proof-of-concept models. The review is significant because it frames biomarker-driven approaches that may enable more precise diagnosis and treatment monitoring across a broad range of neurologic conditions.

Rossini E, Garibaldi M, Hanna MG et al. · Nature reviews. Neurology · (2026) · View on PubMed ↗

Determinants of response to CAR T cell therapy in a multicenter, multi-trial cohort analysis of patients with lymphoma.

This multicenter, multi-trial cohort analysis studied determinants of response to anti-CD19 CAR T therapy—specifically axicabtagene ciloleucel (axi-cel)—in 580 patients with non-Hodgkin lymphoma (NHL). A high proportion of naive-like T cells (CCR7+CD45RA+) was the strongest phenotypic feature associated with prolonged progression-free survival (PFS; HR 0.46, 95% CI 0.31–0.68, P=9.8×10−5). These findings support using CAR T cell phenotypes such as naive-like composition as predictive biomarkers to improve patient selection and CAR T product design.

Budka J, Davis M, Cao S et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Uncovering the transcriptional hallmarks of endothelial cell aging via integrated single-cell analysis.

This integrated single-cell transcriptomics study constructed the Human Aging Endothelial Cell Atlas (HAECA) using harmonized data from over 375,000 human endothelial cells across 12 tissues throughout adulthood. It identifies age-associated transcriptional shifts, including declines in angiogenic gene expression, consistent with endothelial dysfunction during aging. The atlas and findings are significant for mapping molecular hallmarks of endothelial aging and for informing targets to reduce age-related cardiovascular disease risk.

Dobner S, Kleissl L, Tóth F et al. · Nature aging · (2026) · View on PubMed ↗ · Free PDF ↗

Identification of candidate markers for the isolation of neuron-specific extracellular vesicles.

This study developed and validated an approach to identify candidate protein markers for isolating neuron-specific extracellular vesicles (EVs) from biofluids. Using gene expression and EV proteomic data, it selected transmembrane proteins as cell-type EV markers, created a high-purity immuno-isolation workflow, and computationally nominated markers for neurons, astrocytes, oligodendrocytes, and microglia. The work is significant because it advances non-invasive, cell-type–resolved EV biomarker discovery for monitoring brain cell states.

Ter-Ovanesyan D, Whiteman S, Gilboa T et al. · Nature neuroscience · (2026) · View on PubMed ↗ · Free PDF ↗

Computational Peptide Design: Emerging Concepts in Antibiotics, Immunity, and Evolution.

This review surveyed how machine-learning and AI approaches can be used to mine genomes/proteomes (including ancient sequence data) to design functional antimicrobial peptides across evolutionary time. It reports that AI-enabled peptide design can discover new antibiotic peptides active against priority pathogens and can reveal previously unexpected roles for peptides in host immunity. These advances suggest scalable, genome-informed peptide discovery pipelines that could accelerate development of next-generation antibiotics and immunomodulatory peptide therapeutics.

Chen S, Wang X, Li F et al. · Annual review of microbiology · (2026) · View on PubMed ↗ · Free PDF ↗

Interobserver variability in the interpretation of Papanicolaou tests using the Hologic Genius Digital Diagnostics System: detailed analysis of cytology verification in a large academic laboratory.

The study evaluated interobserver variability in interpreting Papanicolaou tests using the Hologic Genius Digital Diagnostics System (HGDDS) in a large academic laboratory, focusing on cytology verification performance among trained users. The key finding was that among 110 ThinPrep cases enriched for LSIL+ (47), unsatisfactory (4), and NILM (59, including 23 with microorganisms), interpretation variability could be quantified in relation to HGDDS training and case categories. This informs how digital pathology workflows and user training affect diagnostic consistency for cervical cancer screening.

Corbin H, Matsko J, Charity T et al. · American journal of clinical pathology · (2026) · View on PubMed ↗

Intron retention regulates STAT2 function and associates with immunotherapy response in lung cancer.

This work studied how alternative splicing of immune-related genes influences response to lung cancer immunotherapy by using long-read RNA sequencing in human primary lung adenocarcinomas. The authors identified retained introns in the STAT2 gene that altered STAT2 protein function and associated with immunotherapy response, linking intron retention to the type I interferon pathway. These findings suggest that STAT2 intron-retention status could serve as a molecular biomarker and mechanistic determinant of checkpoint inhibitor efficacy.

Englander RP, Brugiolo M, Devoucoux M et al. · Science (New York, N.Y.) · (2026) · View on PubMed ↗

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Neurobiology: circuits, pain, sleep, and neuroimmune interactions

De-diagnosis and the problem of revisability in adult ADHD and autism.

This Frontiers in sociology paper studied how adult diagnoses of attention-deficit/hyperactivity disorder (ADHD) and autism have shifted in high-income health systems, emphasizing the “revisability” problem in adult neurodevelopmental diagnostic practice. It argues that adult neurodevelopmental diagnosis has become demand-led and co-produced, identity-conferring rather than merely descriptive, and self-reinforcing rather than static—creating a diagnostic culture that is efficient at conferring diagnoses but weak at ensuring revisability. The work is significant for informing policy and clinical assessment frameworks to improve diagnostic accuracy and the ability to correct or update diagnoses over time.

Adamou M, Hill D · Frontiers in sociology · (2026) · View on PubMed ↗ · Free PDF ↗

Sustained antidepressant-like effects of psychedelics through 5-HT2AR-β-arrestin signaling.

This preclinical study investigated how psychedelics produce sustained antidepressant-like effects in mice, focusing on 5-HT2AR–β-arrestin signaling and receptor kinetics. It finds that lysergic acid diethylamide (LSD) slow dissociation enables progressive 5-HT2AR engagement during repeated low-dose dosing, sustaining β-arrestin signaling while limiting robust Gαq-mediated Ca2+ responses. The results are significant because they suggest a mechanistic route to long-lasting antidepressant effects with reduced hallucinogenic liability via biased 5-HT2AR signaling.

He L, Tang L, Cao D et al. · Nature neuroscience · (2026) · View on PubMed ↗

Behavioral genomics identifies Creld1 as a cross-modal regulator of somatosensation.

This study used an AAV9-mediated postnatal CRISPR-Cas9 knockout platform delivered via single-guide RNAs to interrogate DRG-expressed genes in mice, combined with somatosensory behavioral assays. It reports that a targeted screen of 20 genes identified Creld1 as a cross-modal regulator of somatosensation, supported by either sgRNA-mediated postnatal knockout or tamoxifen-induced Cre recombination. This is significant because it expands the molecular map of somatosensory circuitry and provides a gene-level handle for dissecting modality-spanning sensory regulation.

Jiang Y, Huang W, Yao H et al. · Nature neuroscience · (2026) · View on PubMed ↗

Sensory neuron-derived CGRP ameliorates kidney injury and fibrosis via monocytes and macrophages.

The study investigated how sensory neuron-derived CGRP regulates renal injury and fibrosis by examining renal neuroimmune interactions in models of ischemia-reperfusion (I/R) kidney injury. It found that nociceptive TRPV1+ sensory neurons protect against I/R-induced kidney dysfunction and that CGRP ameliorates kidney injury and fibrosis through effects on monocytes and macrophages. These findings support a neuroimmune therapeutic strategy targeting the CGRP/monocyte-macrophage axis to prevent AKI-to-CKD progression.

Wang L, Li H, Feng J et al. · Cell research · (2026) · View on PubMed ↗ · Free PDF ↗

Chronic stress activates a hypothalamic vagal circuit to promote hepatocellular carcinoma progression in male mice.

The study examined whether chronic stress promotes hepatocellular carcinoma (HCC) progression in male mice by mapping a hypothalamic vagal circuit and identifying tumor–immune signaling mechanisms. It found that chronic stress hyperactivates a glutamatergic paraventricular hypothalamic nucleus to cholinergic dorsal motor nucleus of the vagus pathway, increasing intratumoral acetylcholine, which activates CHRNA9+ epithelial cells and promotes macrophage interaction via COL1A1/2–CD44–STAT3 signaling to drive CXCL1 production and tumor proliferation. This links stress neurobiology to actionable cholinergic/CHRNA9–STAT3 signaling in HCC progression.

Zhang K, Zhang J, Chi D et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

A vagal gut-brain axis for feeding-induced gastric secretion in mice.

This mouse study dissected a vagal gut-brain-gut circuit controlling feeding-induced gastric secretion by using stomach-innervating vagal afferent manipulations. It found that Glp1r+ and Sst+ vagal afferent neurons drove secretion, while Oxtr+ and Vip+ neurons had little effect, and that Piezo2 in Glp1r+ mechanosensory afferents was required for distension-evoked secretion. The work identifies specific vagal neuron types and the Piezo2 mechanotransduction pathway as key regulators of meal-related gastric physiology.

Wang Z, Tang Q, Li K et al. · Neuron · (2026) · View on PubMed ↗

An autonomous macrophage-nociceptor mechanosensory relay drives chronic visceral pain.

This study examined how immune cells transduce mechanical cues into pain signals in colitis-associated visceral hypersensitivity, focusing on Piezo1 in tissue-resident CX3CR1+ macrophages and its downstream effects on nociceptors. It found that macrophage Piezo1 drives calcium influx and NF-κB activation to induce NGF synthesis via occupancy of the Ngf promoter, and that macrophage-derived NGF sensitizes TRPV1+ nociceptive afferents, producing chronic visceral pain. The work is significant because it identifies a specific mechanosensory immune-to-nerve relay (Piezo1→NGF→TRPV1) as a potential therapeutic target for visceral pain in inflammatory bowel disease.

Wu L, Shen T, Wang Z et al. · Science immunology · (2026) · View on PubMed ↗

Neural circuitry mediating hypercapnia-induced microarousal and impaired sleep depth.

The study mapped neural circuitry responsible for intermittent hypercapnia-induced microarousal and reduced sleep depth by focusing on glutamatergic neurons in the nucleus tractus solitarius (NTSVglut2) and their projections in the mouse brain. The key finding was that intermittent hypercapnic air activates NTSVglut2 neurons and that optogenetic or chemogenetic activation of these neurons is sufficient to trigger arousal and impair sleep, with projection-specific activation implicating NTSVglut2 inputs to the paraventricular nucleus (PVN) and parabrachial nucleus (PB). This identifies a mechanistic circuit for hypercapnia-driven sleep fragmentation, informing potential targets for treating sleep disruption in obstructive sleep apnea.

Yang C, Tang WX, Wang WX et al. · Science advances · (2026) · View on PubMed ↗ · Free PDF ↗

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Neurodegeneration and brain biomarkers

Tau isoform mapping across tissues and biofluids reveals a signature distinguishing Alzheimer’s disease from amyotrophic lateral sclerosis.

The study mapped tau isoforms across tissues and biofluids to distinguish Alzheimer’s disease (AD) from amyotrophic lateral sclerosis (ALS) by analyzing serum and brain/spinal cord/muscle samples. It found that direct immunoassays increased blood BD-tau and p-tau217 in both AD and ALS versus controls, but that BD-tau and BD-p-tau217 after BD-Tau immunoprecipitation and targeted mass spectrometry of tissues can better separate AD from ALS by accounting for peripheral (big) tau contributions. This supports more specific blood-based tau biomarkers for clinical differential diagnosis between AD and ALS.

Abu-Rumeileh S, Großkopf H, Guthknecht A et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Blood-Based Biomarkers as Predictors of All-Cause Dementia: A 13-Year Follow-Up in the Whitehall II Cohort Study.

This retrospective analysis in the UK Whitehall II longitudinal cohort assessed whether blood-based biomarkers measured in stored samples (amyloid-beta Aβ42 and Aβ40) predict incident all-cause dementia over 13 years, alone and alongside established risk factors, in community-dwelling older adults. The key finding was the long-term prediction performance of these amyloid-related blood biomarkers for developing all-cause dementia in a heterogeneous population. Clinically, the results inform whether blood amyloid measures can be used for durable dementia risk prediction beyond short-term research settings.

Sabia S, Dumurgier J, Cavaillès C et al. · Neurology · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiovascular therapeutics and device-based interventions

The evolution and future of conduction system pacing.

This review studied the evolution of cardiac pacing strategies in patients with bradyarrhythmias, contrasting conventional right ventricular (RV) apical pacing with conduction system pacing approaches that target the His–Purkinje network. It finds that chronic RV apical pacing can cause ventricular dyssynchrony and pacing-induced cardiomyopathy, whereas His bundle pacing and related conduction system pacing techniques better preserve the native ventricular activation sequence. Clinically, the review supports broader adoption and further technical refinement of conduction system pacing to improve long-term outcomes compared with traditional RV apical pacing.

Lee SR, Vijayaraman P, Huang W et al. · Nature reviews. Cardiology · (2026) · View on PubMed ↗

Arrhythmic events and genetic variants as drivers for Takotsubo Syndrome: a patient-specific atrial stem-cell model.

The study investigated patient-specific arrhythmia mechanisms and genetic variability in Takotsubo Syndrome (TTS) using induced pluripotent stem cell-derived atrial and ventricular cardiomyocytes (iPSC-CMs) from TTS patients, with isoprenaline (isoprenaline/Iso) used to provoke TTS-like events. Compared with controls, atrial TTS iPSC-CMs showed enhanced diastolic sarcoplasmic reticulum (SR) Ca2+ leak and increased arrhythmogenic potential after Iso exposure. These findings support a personalized, atrial Ca2+-handling–driven mechanism for TTS-associated atrial fibrillation risk and provide a platform for mechanism-based risk stratification and therapy testing.

Brand C, Zinke C, Syed Ali G et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Short-term safety, feasibility, and performance of a novel soft robotic biventricular mechanical circulatory support device avoiding blood contact - The MISSION reBEAT trial.

The MISSION reBEAT trial studied a novel soft-robotic biventricular mechanical circulatory support device (reBEAT®) designed to avoid blood contact by externally encircling the heart, in 10 end-stage heart failure patients immediately before elective LVAD implantation. The key findings were short-term safety and feasibility of the device, including individualized assistance enabled by CT-based custom manufacturing to match cardiac anatomy. This is significant because it addresses major limitations of mechanical circulatory support—blood-contact complications and lack of biventricular support—by demonstrating early clinical performance.

Ruhparwar A, Schueler S, Stock U et al. · European journal of heart failure · (2026) · View on PubMed ↗

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Inflammation, immunomodulation, and autoimmune disease therapeutics

Current and Emerging Therapies for Generalized Myasthenia Gravis: Toward Precision Medicine.

This Neurology and Therapy review studied the evolving treatment landscape for generalized myasthenia gravis (MG), focusing on how advances in immunopathogenesis have enabled targeted, mechanism-based immunotherapies beyond corticosteroids and conventional immunosuppressants. It summarizes clinical efficacy, safety, and practical considerations for current and emerging therapies, including issues such as delayed onset, long-term toxicity, and incomplete disease control. The review is significant for supporting precision medicine approaches to treatment selection, sequencing, and real-world decision-making in generalized MG.

Yoshikawa M, Ide T, Koike H · Neurology and therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Autologous erythrocyte microparticles drive antitumour T cell immunity via haem-mediated dendritic cell activation.

This preclinical study examined whether autologous erythrocyte microparticles generated by controlled ultraviolet irradiation can act as vaccine adjuvants to drive anti-tumor T cell immunity in mice. It finds that the microparticles are taken up by dendritic cells, deliver haem cargo to lysosomes and then to the nucleus, and thereby enhance tumor antigen-specific cytotoxic T cell responses and Th1 skewing. The findings are significant as a potential safer adjuvant strategy to improve cytotoxic T cell induction compared with conventional adjuvants.

Tang K, Liang Y, Sun W et al. · Nature biomedical engineering · (2026) · 1 citations · View on PubMed ↗

Extracorporeal photopheresis for the treatment of steroid-refractory immune related adverse events from immune checkpoint inhibitor therapy: a multi-center phase Ib/II clinical trial.

This prospective, single-arm, non-randomized phase Ib/II trial studied extracorporeal photopheresis (ECP) for steroid-refractory immune-related adverse events (irAEs) caused by immune checkpoint inhibitor therapy in 30 cancer patients. The trial met its primary safety endpoint, with less than 50% of patients developing ECP-related severe adverse events and no ECP-related severe adverse events observed. Clinically, the results support ECP as a feasible treatment option for managing refractory ICI-associated toxicities while minimizing additional severe harm.

Riemer R, Braun LM, Giesler S et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Emerging drugs in phase 2/3 and selected phase 1/2 cellular-therapy trials: a glimpse into the future of systemic sclerosis treatment.

This review evaluated emerging systemic sclerosis (SSc) therapies by summarizing drugs in phase 2/3 and selected phase 1/2 cellular-therapy trials, alongside context from existing organ-specific treatments such as tocilizumab and nintedanib. It concludes that while multiple targeted agents are under investigation for specific manifestations, there remains a lack of approved therapies that treat overall disease comprehensively. The article is clinically important because it maps the near-term therapeutic pipeline for SSc and highlights where future trials and targets may be needed.

Naveed E, Lescoat A, Matucci-Cerinic M et al. · Annals of the rheumatic diseases · (2026) · View on PubMed ↗ · Free PDF ↗

Serine protease inhibitor A3 is a soluble SIRPα ligand that suppresses inflammation and antitumor immunity.

This study investigated whether human SERPINA3 and its mouse ortholog SERPINA3k act as soluble ligands for the inhibitory receptor SIRPα and assessed their immunologic and therapeutic effects in vivo. It reports that SERPINA3/SERPINA3k bind and activate SIRPα to suppress SIRPα+ macrophages, neutrophils, dendritic cells, and NK cells, alleviating LPS-induced pneumonia and improving models of experimental autoimmune encephalomyelitis and rheumatoid arthritis, while a SERPINA3D2 mutant retains SIRPα interaction but reduces adverse effects. The significance is that SERPINA3-family proteins (and engineered mutants) may represent a tractable immunomodulatory strategy to dampen inflammation and antitumor immune suppression via SIRPα signaling.

Hou Y, Huang L, Jin C et al. · Nature immunology · (2026) · View on PubMed ↗

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Clinical trials and guidelines in non-oncology diseases (infectious, endocrine/bone, hematology, liver, etc.)

14-day versus 28-day trifluridine-tipiracil plus bevacizumab for refractory metastatic colorectal cancer (PRABITAS): a pragmatic, multicentre, open-label, randomised, phase 3, non-inferiority trial in Japan.

PRABITAS studied whether a simplified 14-day schedule of trifluridine-tipiracil (FTD-TPI) plus bevacizumab is non-inferior to the conventional 28-day schedule for overall survival in Japanese patients with refractory metastatic colorectal cancer. The trial was designed to test survival preservation while addressing clinically significant hematological and gastrointestinal toxicity associated with the standard schedule. If non-inferiority is demonstrated, the 14-day FTD-TPI/bevacizumab regimen could become a less toxic, more patient-friendly standard option in this population.

Sakakida T, Taniguchi H, Asayama M et al. · Lancet (London, England) · (2026) · View on PubMed ↗

Skeletal effects of GLP-1 receptor agonist therapy in adults with overweight or obesity: a systematic review.

This Archives of Osteoporosis systematic review studied skeletal effects of glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in adults with overweight or obesity using data from eight randomized controlled trials (n=493). Across trials, bone mineral density outcomes were assessed by DXA, but results were not pooled because the trials evaluated four pharmacologically distinct GLP-1 RAs with markedly different weight-loss potency. The review concludes that evidence is sparse for each agent and insufficient to establish definitive skeletal effects in this population, highlighting a need for more agent-specific, bone-focused trials.

Lai CH, Li YT, Wu TS et al. · Archives of osteoporosis · (2026) · View on PubMed ↗

Epidemiology, Risk Factors, and Prevention of Prostate Cancer.

This narrative review assessed geographical differences and temporal trends in prostate cancer incidence and mortality, and summarized prostate cancer risk factors, using GLOBOCAN 2024 estimates for 185 countries with projections to 2050. It finds substantial regional variation in prostate cancer burden driven by differences in risk factors, screening, management, and access to care, with projected future trends dependent on the assumption that 2024 age-specific rates remain unchanged. The work is significant for guiding region-specific prevention and screening strategies to reduce prostate cancer morbidity and mortality.

Gandaglia G, Weiner AB, Briganti A et al. · European urology · (2026) · View on PubMed ↗

Reduced Risk of MASLD and Cardiometabolic Disease Following Renal Denervation Therapy in Patients With Resistant Hypertension.

This target trial emulation used the TriNetX global federated health research network to compare renal denervation versus intensive antihypertensive therapy in patients with resistant hypertension, assessing downstream cardiometabolic outcomes including MASLD risk. It finds that renal denervation is associated with a reduced risk of metabolic dysfunction-associated steatotic liver disease (MASLD) and broader cardiometabolic disease compared with intensive medical therapy. The results are clinically significant because they suggest renal denervation may confer benefits beyond blood pressure reduction by modulating autonomic pathways linked to cardio-kidney-metabolic risk.

Henney AE, Anson M, Riley DR et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

Clinical heterogeneity in chronic inflammatory demyelinating polyneuropathy: data-driven subtypes challenge current classification.

This multicenter retrospective observational study used data-driven unbiased clustering to identify clinically meaningful subtypes of chronic inflammatory demyelinating polyneuropathy (CIDP) in 425 patients from 10 German centers, with 325 in a discovery cohort and 100 in validation. It reports that clinical heterogeneity in CIDP can be captured by newly derived data-driven subgroups that challenge the adequacy of current CIDP classifications. This is significant because refined CIDP subtypes could improve prognostication and guide more tailored treatment decisions.

Quint P, Kohle F, Oeztuerk M et al. · Journal of neurology · (2026) · View on PubMed ↗ · Free PDF ↗

Inducible chronic NAD deficiency in mice reveals multi-systemic phenotypical, metabolic, and transcriptional changes.

The study used acquired niacin dependency (ANDY) mice to induce chronic NAD deficiency and characterize multi-system phenotypic, metabolic, and transcriptional changes. It found that a niacin-free diet caused widespread tissue NAD depletion and sex-independent abnormalities including kyphosis, reduced bone and body mass, impaired exercise capacity, frailty, cataracts, and disrupted energy homeostasis. This provides an in vivo platform for understanding how chronic NAD loss drives systemic disease and for testing NAD-restoring interventions.

Benitez-Rosendo A, Feuz MB, Chini CCS et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗

Firstline treatment with ruxolitinib versus best available therapy in patients with polycythemia vera: results from the randomized RuxoBEAT trial.

The study compared first-line ruxolitinib (RUX) versus best available therapy (BAT) in patients with polycythemia vera (PV) in the randomized RuxoBEAT trial. It found that the primary endpoint—clinico-hematologic complete response at month 6—was not met (2.3% with RUX vs 2.9% with BAT), while secondary/exploratory analyses showed RUX was more effective than BAT at improving hematocrit and splenomegaly. These results inform the relative benefit of initiating ruxolitinib earlier in PV treatment compared with standard best available approaches.

Koschmieder S, Isfort S, Teichmann LL et al. · Blood cancer journal · (2026) · View on PubMed ↗ · Free PDF ↗

PET-Guided Dose Escalation for Stage III Non-Small Cell Lung Cancer: A Randomized Clinical Trial.

The PET-BOOST randomized phase 2 trial studied whether fluorodeoxyglucose (FDG)-PET-guided dose escalation to metabolically active tumor subvolumes improves outcomes in inoperable FDG-avid stage IIIA/IIIB non-small cell lung cancer (NSCLC) compared with standard chemoradiation. The key finding reported in the abstract is the trial’s design and evaluation of PET-guided boost dosing (achievable boost dose ≥65 Gy) to reduce locoregional failure, with results pending in the truncated text. Clinically, if effective, PET-guided escalation could enable more individualized radiotherapy that targets metabolically active disease while limiting overtreatment of non-boost regions.

Raman S, Bissonnette JP, Palma DA et al. · International journal of radiation oncology, biology, physics · (2026) · View on PubMed ↗

Pharmacotherapy for MASLD: current evidence and challenges in clinical practice.

This review summarized current evidence and practical challenges for pharmacotherapy in metabolic dysfunction-associated steatotic liver disease (MASLD), focusing on the rapidly expanding drug development pipeline and clinical implementation barriers. The key finding is that only resmetirom and semaglutide are currently conditionally approved for patients with fibrosis, while multiple emerging therapies will require improved patient selection to maximize benefit. Scientifically and clinically, it highlights the need for better biomarkers/stratification strategies as new MASLD drugs enter practice.

Pages L, Rojo D, Jimenez-Masip A et al. · Annals of hepatology · (2026) · View on PubMed ↗ · Free PDF ↗

Cavitary status and differential treatment response in refractory or severe Mycobacterium avium complex pulmonary disease: Amikacin liposome inhalation suspension versus intravenous amikacin.

This retrospective chart review compared culture conversion outcomes in 57 patients with refractory or severe Mycobacterium avium complex pulmonary disease (MAC-PD) treated with amikacin liposome inhalation suspension (ALIS) versus intravenous amikacin (IV AMK), stratified by cavitary status. ALIS and IV AMK differed in culture conversion depending on whether patients had cavitary disease (with the study specifically assessing whether cavity status modified treatment response). Clinically, this helps guide selection of intensified aminoglycoside therapy in refractory/severe MAC-PD by incorporating cavitary status into treatment decisions.

Hayashi M, Shimizu S, Furuta A et al. · Respiratory medicine · (2026) · View on PubMed ↗

Remibrutinib versus teriflunomide in relapsing multiple sclerosis (REMODEL-1 and REMODEL-2): two randomised, phase 3 trials.

These two phase 3 randomized, double-blind, double-dummy trials (REMODEL-1 and REMODEL-2) studied remibrutinib versus teriflunomide in adults with relapsing multiple sclerosis (aged 18–55, EDSS 0–5·5, with recent disease activity). Remibrutinib demonstrated efficacy and safety outcomes compared with teriflunomide as an active comparator across the event-driven trial designs. The findings are clinically important because they evaluate a CNS-penetrant covalent BTK inhibitor (remibrutinib) as a potential new oral disease-modifying therapy for relapsing MS.

Wiendl H, Bermel R, Airas L et al. · Lancet (London, England) · (2026) · View on PubMed ↗ · Free PDF ↗

Perioperative chemotherapy and stereotactic body radiotherapy versus perioperative chemotherapy alone in patients with high-risk, localised pancreatic cancer (MASTERPLAN): an open-label, phase 2, multicentre, randomised trial of the Australasian Gastro-Intestinal Trials Group.

This open-label, phase 2 multicentre randomized trial (MASTERPLAN) studied whether adding stereotactic body radiotherapy (SBRT) to perioperative chemotherapy reduces locoregional recurrence in adults with high-risk, localized pancreatic ductal adenocarcinoma (PDAC). The trial compared perioperative chemotherapy plus SBRT versus perioperative chemotherapy alone across 14 hospitals in Australia and New Zealand. If SBRT improves control, it would provide a clinically actionable strategy to reduce locoregional recurrence in a high-risk PDAC population.

Oar A, Kneebone A, Sjoquist KM et al. · The Lancet. Oncology · (2026) · View on PubMed ↗

Efficacy and safety of mitapivat in patients with sickle cell disease (RISE UP): a phase 3, double-blind, global, randomised, placebo-controlled trial.

This phase 3, double-blind, global randomized placebo-controlled trial (RISE UP) evaluated mitapivat, an oral allosteric pyruvate kinase activator, in patients older than 16 years with sickle cell disease who had anemia and recurrent vaso-occlusive pain crises. The study compared mitapivat 100 mg twice daily versus placebo to determine efficacy and safety across multiple international sites. If effective and safe, mitapivat could become a disease-modifying option targeting hemolysis and sickling biology in sickle cell disease.

Andemariam B, Kuo KHM, Algahtani FH et al. · Lancet (London, England) · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗

Which Fellowship Experiences Matter Most? A Graduate Survey of Perceived Training Value.

The study surveyed Hospice and Palliative Medicine (HPM) fellowship graduates from The University of Texas MD Anderson Cancer Center (2001–2024) to determine which fellowship experiences they perceived as most valuable. The key finding was that among 68 completed surveys (62% response rate), most graduates reported ongoing clinical practice in palliative medicine and rated specific training components (e.g., didactic lectures and clinical rotations) as particularly valuable. This provides actionable feedback for optimizing HPM fellowship curricula to better align training experiences with graduate-perceived educational value.

Singleton GA, Azhar A, Baez Gonzalez J et al. · The American journal of hospice & palliative care · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on October 25, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.