PubMed Trending Research Digest — June 02, 2026

Automated digest · 96 articles · 15 research areas · June 02, 2026

Overview

Across this week’s set of papers, a dominant theme is precision targeting—both in oncology and in immune/inflammatory disease—using increasingly specific biomarkers, engineered delivery systems, and mechanism-led combinations. Multiple phase 2/3 trials test targeted agents (e.g., IGF-1R blockade for thyroid eye disease, FGFR2 inhibition in cholangiocarcinoma, RET inhibition in early NSCLC, RAS(ON) inhibition in pancreatic cancer, and MET/SEZ6-directed strategies in gastric cancer and solid tumors). In parallel, immunotherapy studies extend beyond checkpoint blockade to include individualized neoantigen vaccination and TCR-based or myeloid-reprogramming approaches for “cold” tumors, while mechanistic work (single-cell/multi-omic and modeling) clarifies how resistance emerges through both genetic evolution and non-genetic state shifts.

A second major thread is inflammation and immune regulation at the interface of systems biology and therapeutics. Studies span gut-lung and gut-immune axes (microbiota-dependent sepsis-ARDS protection; macrophage polarization control in colitis; thymic regulation of Tregs in IBD), complement-mediated rescue in NMOSD, and metabolic-epigenetic control of inflammatory signaling (e.g., PRMT1–LDHA–STAT3 lactylation; aspartate metabolism tuning cGAS–STING interferon responses). Several papers also emphasize engineered or biomaterial-like interventions—such as macrophage-targeted circRNA nanoparticles for aged bone, and programmable “Btbots” that sense inflammation biomarkers to deliver anti-inflammatory payloads—highlighting a shift toward responsive, localized immunomodulation rather than systemic treatment alone.

Finally, multiple contributions focus on risk prediction, real-world implementation, and long-term safety/monitoring. Large cohort analyses and multi-omics “aging” clocks (LE8, AIP/modified AIP, Liver Aging Index, StackAge) aim to stratify future disease trajectories and support earlier prevention. Health-policy and pharmacovigilance work addresses biosimilar adoption and vaccine safety signals, while clinical and economic studies evaluate perioperative outcomes, screening strategies, and cost-effectiveness. Complementing these, gene-therapy safety review work underscores the importance of vector-specific persistence/integration assumptions and continued long-term monitoring for rAAV therapies.

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Gene therapy safety & vector biology

Beyond the Gut: How the Thymus Reshapes the Immune Landscape of Inflammatory Bowel Disease.

This Comprehensive Physiology review summarized how the thymus reshapes the immune landscape in inflammatory bowel disease (IBD), focusing on thymic control of regulatory T cells (Tregs) and intestinal immune homeostasis. The key finding is that thymic microenvironmental cues, transcription factors, and signaling pathways can influence Treg development/function, thereby modulating IBD pathogenesis and immune dysregulation. This is significant because it highlights the thymus as a mechanistic upstream regulator and suggests new avenues for immune-targeted strategies in IBD.

Ma Y, Liu H, Zhang Z et al. · Comprehensive Physiology · (2026) · View on PubMed ↗

Adeno-Associated Virus Gene Therapy: Is There a Risk of Insertional Mutagenesis?

This article reviewed the long-term safety of recombinant adeno-associated virus (rAAV) gene therapy, focusing on insertional mutagenesis risk by comparing wild-type AAV (wtAAV) persistence and integration behavior in host tissues. It concludes that while wtAAV can integrate into the genome and clonal wtAAV integration has been reported in a small number of hepatocellular carcinoma cases, the risk appears to be minor and is difficult to directly extrapolate to rAAV because vector structure and persistence differ. The significance is that ongoing long-term monitoring and risk assessment for AAV therapies should account for episomal persistence and vector-specific differences rather than assuming wtAAV integration rates translate directly to rAAV.

Batty P · Toxicologic pathology · (2026) · View on PubMed ↗ · Free PDF ↗

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Cell-based biomaterials & regenerative immunomodulation

Engineered Bacteroides thetaiotaomicron sense gut inflammation and deliver therapeutic molecules to alleviate colitis in mice.

This preclinical study engineered the human gut commensal bacterium Bacteroides thetaiotaomicron into programmable “Btbots” to sense intestinal inflammation biomarkers and deliver anti-inflammatory therapeutics in mouse colitis models. The key finding was that chromosomally integrated genetic circuits enabled Btbots to detect two inflammation biomarkers—deoxycholic acid (DCA) and nitric oxide (NO)—and enhance targeted therapeutic delivery to alleviate colitis. This is scientifically significant because it demonstrates a colonizing, biomarker-responsive microbial platform for precision delivery of therapeutics in inflammatory bowel disease.

Ye M, Liu X, Peng Z et al. · Nature microbiology · (2026) · View on PubMed ↗

Insights into the therapeutic strategies for aging and aging-associated diseases.

This review article synthesized current therapeutic strategies aimed at hallmarks of aging and aging-associated diseases, focusing on interventions targeting cellular senescence, metabolic dysfunction, epigenetic alterations, and mitochondrial impairment. It highlights three main therapeutic approaches—senolytics (e.g., dasatinib plus quercetin), senomorphics (e.g., rapamycin), and senescence-targeting immunotherapies—along with emerging mechanistic and translational advances. The significance is that it provides an organized framework for developing and prioritizing interventions that may delay aging and reduce risk of multiple age-related conditions.

Dong R, Wu Q, Kan J et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗

In vivo circRNA-engineered macrophages mediate localized MMP9 neutralization to rejuvenate aged bone.

The study developed an in vivo circular RNA (circRNA)-engineered macrophage platform to neutralize matrix metalloproteinase-9 (MMP9) and tested it in the context of aged bone, using transcriptomics from older patients to motivate targeting MMP9. It engineered apoptosis-mimicking phosphatidylserine-containing lipid nanoparticles (aMMP9-LNP) to deliver circRNA-based antibody engineering that enhances macrophage-specific recognition/endocytosis and local MMP9 neutralization to rejuvenate aged bone. This provides a macrophage-targeted immunotherapy concept for age-associated bone degeneration by locally suppressing MMP9-driven pathology.

Zhu D, Ling S, Fang H et al. · Bioactive materials · (2026) · View on PubMed ↗ · Free PDF ↗

Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs) and Small Intestinal Submucosa (SIS) Hydrogel Composite Can Meliorate TNBS-Induced Experimental Colitis Through Regulating Inhibiting Macrophage Polarization Toward the M1 Phenotype.

This study tested whether a composite of small intestinal submucosa (SIS) hydrogel plus bone marrow-derived mesenchymal stem cells (BM-MSCs) can ameliorate 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis by modulating macrophage polarization in mice and RAW264.7 macrophages in vitro. The key finding is that the MSC-SIS conditioned system regulates macrophage polarization away from the pro-inflammatory M1 phenotype (with effects assessed using macrophage polarization markers such as CD206 and proliferation via clone formation assays). Clinically, this supports BM-MSC/SIS hydrogel composites as a potential cell-based biomaterial strategy for inflammatory bowel disease by targeting macrophage M1/M2 balance.

Sun Z, Zhou Y, Geng X et al. · Mediators of inflammation · (2026) · View on PubMed ↗ · Free PDF ↗

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Circadian biology & sarcopenia

Restoration of circadian rhythm as novel targets against sarcopenia.

This narrative review examined how restoring circadian rhythm could serve as a novel therapeutic target for sarcopenia, an age-related decline in skeletal muscle mass, strength, and function. It highlights disrupted circadian rhythms as a driver of pathways including protein remodeling, insulin resistance, and mitochondrial function, alongside systemic chronic low-grade inflammation (SCLGI), as key mechanistic contributors. The significance is that circadian-based interventions may represent a new drug-development direction for sarcopenia in the absence of FDA-approved disease-modifying therapies.

Wang T, Hong Z · Chinese medical journal · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiometabolic risk indices & multimorbidity prediction

Identification of Novel Genetic Risk Variants Associated With Early-Onset Ischemic Stroke in Taiwan.

This study performed genome-wide association analyses to identify genetic risk variants for early-onset ischemic stroke (ages 18–54) in a Han-ethnicity Taiwanese population using the Taiwan Precision Medicine Initiative database. The key finding was the identification of novel common and rare genetic risk variants associated with early-onset ischemic stroke, followed by fine-mapping and linkage disequilibrium analyses to assess functional relevance. This is significant because it improves understanding of stroke genetics in younger patients and may enable population-specific risk prediction and mechanistic discovery.

Wang YC, Liu KM, Gan YL et al. · Neurology · (2026) · View on PubMed ↗

Role of Physical Activity in Obesity Treatment and Cardiometabolic Health: A Scientific Statement From the American Heart Association.

This American Heart Association scientific statement reviewed evidence on how physical activity contributes to obesity treatment and cardiometabolic health, including effects on weight loss, weight-loss maintenance, and cardiometabolic risk factors independent of weight change. It concluded that exercise and physical activity improve major risk factors such as hypertension, insulin resistance, and dyslipidemia and should complement lifestyle, pharmacologic, and surgical weight-loss interventions. The statement is significant for clinicians because it provides an evidence-based framework for integrating physical activity into comprehensive obesity and cardiovascular risk management.

Swift DL, Ross LM, Laddu DR et al. · Circulation · (2026) · View on PubMed ↗

Associations of the atherogenic index of plasma and its modified indices with the incidence and progression of cardiovascular-liver-metabolic multimorbidity: a prospective cohort study from UK Biobank.

This prospective cohort study in 370,258 UK Biobank participants without baseline cardiovascular-liver-metabolic (CLM) diseases assessed whether the atherogenic index of plasma (AIP) and seven modified AIP indices predicted incidence and progression of cardiovascular-liver-metabolic multimorbidity (CLMM). The key finding was that higher AIP and certain modified AIP measures were associated with greater risk of developing and progressing CLMM, with biomarker analyses suggesting partial explanatory pathways. These results support AIP-based lipid–adiposity metrics as practical risk stratification tools for CLMM and motivate biomarker-targeted prevention strategies.

He Q, Sun M, Yao J et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗

Faster CYP2A6 increases COPD and lung cancer risk by increasing smoking quantity: a mediated mendelian randomization and observational mediation study.

This study used two-step two-sample mediated Mendelian randomization and observational mediation to test whether smoking quantity mediates the association between CYP2A6 activity and risks of chronic obstructive pulmonary disease (COPD) and lung cancer (LC). The key finding was that faster CYP2A6 activity increased COPD and LC risk primarily by increasing smoking quantity (e.g., pack-years and cigarettes per day), with mediation differing by disease outcome. The clinical significance is that CYP2A6-driven nicotine metabolism may influence disease risk through modifiable smoking exposure, informing risk prediction and potentially targeted smoking-cessation interventions.

Giratallah H, Chenoweth MJ, Lerman C et al. · Respiratory research · (2026) · View on PubMed ↗ · Free PDF ↗

Dietary bioactive compounds modulating satiety and appetite: mechanisms of action.

This article reviewed molecular and physiological mechanisms by which dietary bioactive compounds modulate satiety and appetite, focusing on gastrointestinal hormones (GLP-1, CCK, PYY, ghrelin), hypothalamic pathways, and microbial metabolites such as short-chain fatty acids (SCFAs). The key finding was that multiple compound classes (including fibers, proteins, lipids, and polyphenols) converge on hormone secretion, neural appetite regulation, and gut–microbiome signaling to influence energy intake. Scientifically, the synthesis clarifies mechanistic targets for developing diet-based or nutraceutical approaches to obesity and metabolic disease management.

Casado-Hidalgo G, Pueyo-Arias M, Gil-Cardoso K et al. · Journal of physiology and biochemistry · (2026) · View on PubMed ↗

The Impact of GLP-1-Based Therapies on Cardiovascular Outcomes in Type 2 Diabetes: A Comprehensive Systematic Review and Network Meta-Analysis.

This systematic review and frequentist random-effects network meta-analysis compared GLP-1-based therapies for cardiovascular outcomes in adults with type 2 diabetes mellitus (T2DM) using hazard ratio (HR)-based evidence from randomized controlled trials. The key finding was that different GLP-1-based agents showed distinct comparative effects on time-to-event outcomes including all-cause mortality, cardiovascular mortality, MACE, non-fatal myocardial infarction, and non-fatal stroke. The significance is that agent-level comparative estimates can guide evidence-based selection of GLP-1 therapies to reduce cardiovascular risk in T2DM.

Chuang SM, Liu SC, Chien KL et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗

Do GLP-1 Receptor Agonists Sabotage Fat Grafts? : A Scoping Review of GLP-1 Receptor Agonist Effects on Adipocyte Biology and Implications for Autologous Fat Transfer.

This scoping review synthesized preclinical and clinical evidence on whether GLP-1 receptor agonists (GLP-1 RAs) could impair adipocyte biology relevant to fat graft survival, with implications for autologous fat transfer. The key finding was that GLP-1 RA effects on adipocyte function and metabolism may be potentially antagonistic to mechanisms required for graft take, though the evidence base is still emerging and heterogeneous. Clinically, the review highlights the need for careful perioperative management and further studies to determine how GLP-1 RA exposure affects outcomes of autologous fat grafting.

Chalhoub X, Yang Ng Z · Aesthetic surgery journal · (2026) · View on PubMed ↗ · Free PDF ↗

12‑weeks fisetin supplementation and interval resistance with aerobic training: changes in Maresin‑1 and inflammatory markers in men with obesity: a randomized controlled trial.

This 12-week parallel-group randomized controlled trial in 44 obese men (BMI > 30 kg/m²) tested whether fisetin supplementation (200 mg/day) combined with interval resistance-aerobic training changes Maresin-1 (MaR1) and inflammatory markers. The key finding was that fisetin plus training modulated MaR1 and inflammatory markers compared with control, with implications for improved metabolic/inflammatory status and insulin resistance. Clinically, it suggests a potential nutraceutical adjunct to exercise for reducing obesity-related inflammation.

Alipour M, Saeidi A, Hejazi K et al. · Journal of the International Society of Sports Nutrition · (2026) · View on PubMed ↗ · Free PDF ↗

Liver Aging Index: A Noninvasive Score for Liver Biological Aging and Liver-Related Outcomes in Multicohorts.

This multicohort study developed the Liver Aging Index (LAI), a noninvasive score of liver biological aging, using data from the China Kadoorie Biobank (CKB; N=21,629) with a Cox-Gompertz proportional hazards model. The key finding was that LAI combined clinical factors (BMI, systolic/diastolic blood pressure), plasma biomarkers (including liver enzymes and lipid/glucose measures), and imaging biomarkers (fat attenuation parameter and liver stiffness measurement) to predict liver-related outcomes and biological aging. Clinically, LAI could enable risk stratification and monitoring of liver aging without invasive procedures.

Wu Z, Wu S, Song S et al. · Aging cell · (2026) · View on PubMed ↗ · Free PDF ↗

StackAge: an ensemble-based clock for precise quantification of biological age using multi-omics data.

This study developed StackAge, an ensemble-based biological aging clock using multi-omics plasma proteomics and metabolomics from 30,376 UK Biobank participants. StackAge predicted chronological age with high accuracy (Pearson r ~0.93) and improved risk prediction for 12 chronic diseases, with AUCs >0.90 for type 2 diabetes, Alzheimer’s disease, and chronic kidney disease. The approach provides a clinically useful, multi-omics-derived measure of biological age for earlier risk stratification and intervention.

Jiang Y, Jia L, Fei Y et al. · Briefings in bioinformatics · (2026) · View on PubMed ↗ · Free PDF ↗

Remodelling of cystic fibrosis respiratory microbiota in response to extended elexacaftor-tezacaftor-ivacaftor therapy.

This multistate prospective cohort analysis used UK Biobank data (n=391,384) to evaluate whether Life’s Essential 8 (LE8) predicts the incidence of first chronic lung disease (FCLD), progression to chronic lung multimorbidity (CLM), and mortality, and to determine which LE8 components matter most. The key finding is that higher LE8 score is associated with a more favorable trajectory of chronic lung disease development and progression across multistate transitions (from no CLD to FCLD, then to CLM, and ultimately mortality). Scientifically and clinically, it suggests that global cardiovascular/health metrics captured by LE8 may help stratify risk and guide prevention strategies for chronic lung disease progression.

Gavillet H, Hatfield LR, Hardman M et al. · Microbiome · (2026) · View on PubMed ↗ · Free PDF ↗

Biosimilars of anti-VEGF agents in retinal diseases: a narrative review of regulatory, clinical, and pharmacoeconomic aspects.

This multistate analysis of a prospective UK Biobank cohort assessed how Life’s Essential 8 (LE8) relates to the incidence and progression trajectory of chronic lung diseases, including progression to chronic lung multimorbidity (CLM) and subsequent mortality. Using a multistate model, it found that LE8 score is associated with dynamic transitions between lung disease states, indicating that overall LE8 health status tracks with risk of developing and accumulating chronic lung conditions. The significance is that LE8 could be used for risk stratification and prevention planning for chronic lung disease trajectories, potentially informing targeted interventions before multimorbidity develops.

Zong Y, Fan Q, Huang L · International journal of retina and vitreous · (2026) · View on PubMed ↗ · Free PDF ↗

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Biosimilars & regulatory/health-economics for biologics

Semaglutide Injection in Indian Patients With Type 2 Diabetes Mellitus: A Randomised, Phase III, Active-Controlled Study.

This phase III, randomized, open-label, multi-center, active-controlled non-inferiority trial studied semaglutide injection (test product) versus reference semaglutide (Ozempic) in Indian adults with type 2 diabetes mellitus (HbA1c 7.0–10.5%) on stable metformin. The key results reported in the abstract were efficacy, safety, and immunogenicity outcomes over 24 weeks, comparing the test and reference semaglutide formulations (specific numeric outcomes are truncated). Scientifically and clinically, demonstrating comparable efficacy/safety and immunogenicity supports interchangeability of semaglutide products in the Indian T2DM population.

Ambika Gopalakrishnan U, Joshi AS, Giri R et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗ · Free PDF ↗

Pharmacokinetic Model Based Sensitivity Analysis to Lower Recruitment Burden for Young Children Requiring Intravenous Immunoglobulin G Replacement.

This pharmacometrics study used model-informed drug development and sensitivity analysis to reduce recruitment burden in a phase 4 pediatric study for children aged 2–16 years requiring intravenous immunoglobulin G (IVIG) replacement, focusing on Immune Globulin Intravenous 10% Liquid (BIVIGAM). The key finding was that a PK model incorporating age and body weight could characterize total IgG exposure and support simulation-based exposure comparisons between pediatric and adult subjects, enabling more efficient study design. Scientifically and operationally, this approach can improve feasibility of pediatric PK assessments in primary immune deficiency (PID) populations under age 6.

Dumas T, Mehr S, Avila R et al. · CPT: pharmacometrics & systems pharmacology · (2026) · View on PubMed ↗ · Free PDF ↗

Life’s Essential 8 and the incidence and progression trajectory of chronic lung diseases: A multistate analysis of a prospective cohort study.

This narrative review synthesized regulatory, clinical, and pharmacoeconomic considerations for biosimilars of anti-VEGF agents used in retinal diseases such as neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion. It reports that biosimilar adoption is supported by regulatory frameworks from the FDA, EMA, and NMPA and by evidence requirements for demonstrating clinical equivalence and practical interchangeability after patent expirations of ranibizumab and aflibercept. The significance is that it provides a consolidated evidence-and-policy roadmap to help clinicians integrate anti-VEGF biosimilars safely and cost-effectively into retinal care.

Zou Y, Zhang L, Li Y et al. · Chinese medical journal · (2026) · View on PubMed ↗ · Free PDF ↗

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Targeted therapies in solid tumors (phase 2/3 trials)

Savolitinib in MET-amplified gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial.

This open-label, multicenter phase 2 trial evaluated savolitinib, an oral MET inhibitor, in patients with MET-amplified (METamp; gene copy number ≥10 for the pivotal phase) locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma after progression on prior therapy. The study found clinical activity and tolerability of savolitinib in this METamp population, supporting its potential as a targeted option where effective MET-directed therapies have been limited. These results are clinically significant because they help establish evidence for MET inhibition in METamp G/GEJ cancer and may guide biomarker-driven treatment selection.

Peng Z, Liu T, Wang H et al. · Nature medicine · (2026) · View on PubMed ↗

SEZ6-targeting antibody-drug conjugate ABBV-706 in advanced small cell lung cancer and solid tumors: a phase 1 trial.

This phase 1 trial studied ABBV-706, a SEZ6-targeting antibody-drug conjugate that links a SEZ6-directed antibody to a topoisomerase-1 inhibitor (Top1i), in 288 patients with advanced solid tumors including 124 with relapsed/refractory small cell lung cancer (SCLC). The key finding was that SEZ6-directed delivery of a Top1i payload via the antibody-drug conjugate was administered across dose-escalation/optimization/expansion cohorts to evaluate safety and tolerability, with monotherapy given every 3 weeks (Q3W). If efficacy and manageable toxicity are demonstrated, ABBV-706 could represent a targeted ADC strategy for SEZ6-expressing SCLC and related neuroendocrine tumors.

Byers LA, Cho BC, Cooper AJ et al. · Nature medicine · (2026) · View on PubMed ↗

Fovinaciclib for First-Line Therapy of Advanced Breast Cancer: A Randomized Clinical Trial.

This double-blind, phase 3 randomized clinical trial evaluated fovinaciclib plus an aromatase inhibitor as first-line therapy in adult women with hormone receptor-positive, ERBB2-negative advanced breast cancer. The study’s key finding was the comparative efficacy and safety of adding fovinaciclib (a cyclin-dependent kinase inhibitor) to endocrine therapy in this treatment-naïve advanced population. If the trial demonstrates improved outcomes with acceptable toxicity, it would support a new combination strategy for HR+/HER2− advanced breast cancer in the first-line setting.

Yuan P, Liu Y, Li W et al. · JAMA oncology · (2026) · View on PubMed ↗

Antibody-Drug Conjugates for Locally Advanced and Metastatic Urothelial Carcinoma: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis synthesized interventional and observational evidence on antibody-drug conjugates (ADCs) for locally advanced or metastatic urothelial carcinoma (la/mUC), focusing on enfortumab vedotin, disitamab vedotin, and sacituzumab govitecan. It evaluated comparative clinical outcomes and used meta-regression to identify clinical covariates driving heterogeneity in ADC effectiveness and positioning. The findings aim to clarify how these ADCs translate across real-world settings and which patient or treatment factors modify benefit.

Zhang W, Wu H, Wang L et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

THRIVE: A Phase 3, Randomized, Double-Masked, Placebo-Controlled Study of Veligrotug for Active Thyroid Eye Disease.

This phase 3, randomized, double-masked, placebo-controlled THRIVE trial studied veligrotug, a full antagonist monoclonal antibody to the insulin-like growth factor-1 receptor (IGF-1R), in adults with moderate-to-severe active thyroid eye disease (onset ≤15 months, proptosis ≥3 mm, CAS ≥3). The study evaluated whether 10 mg/kg veligrotug improves efficacy and safety versus placebo in this defined active TED population. If effective, IGF-1R blockade with veligrotug could provide a targeted immunomodulatory option for patients with active TED who have unmet therapeutic needs.

Yen MT, Cockerham K, Saeed P et al. · Ophthalmology · (2026) · View on PubMed ↗

Pemigatinib for Unresectable or Metastatic Cholangiocarcinoma With Fibroblast Growth Factor Receptor-2 Rearrangement: Results From the Phase 3 FIGHT-302 Trial.

The phase 3 FIGHT-302 trial assessed first-line pemigatinib, an FGFR1-3 inhibitor, in adults with advanced unresectable or metastatic cholangiocarcinoma harboring FGFR2 rearrangements. Patients were randomized to pemigatinib (13.5 mg once daily) versus gemcitabine plus cisplatin chemotherapy, with efficacy and safety outcomes reported for this FGFR2-rearranged population. Demonstrating benefit would support pemigatinib as a standard first-line targeted therapy for FGFR2-rearranged cholangiocarcinoma.

Bekaii-Saab TS, Melisi D, Wilmink H et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

EP4 Antagonist ONO-4578 Plus Nivolumab and Chemotherapy in HER2-Negative Unresectable Advanced or Recurrent Gastric or Gastroesophageal Junction Cancer.

This multicenter, double-blind, randomized phase 2 trial tested the EP4 antagonist ONO-4578 added to nivolumab plus chemotherapy in chemotherapy-naïve patients with HER2-negative unresectable advanced or recurrent gastric or gastroesophageal junction cancer. The key question was whether ONO-4578 enhances the efficacy of nivolumab plus chemotherapy compared with placebo plus the same backbone regimen. A positive result would validate targeting the PGE2–EP4 immunosuppressive axis as an augmentation strategy in HER2-negative gastric/GEJ cancer.

Nakayama I, Ryu MH, Lim SH et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

Selpercatinib in Early-Stage RET Fusion-Positive Non-Small-Cell Lung Cancer.

This phase 3, double-blind trial studied adjuvant selpercatinib, a CNS-penetrant selective RET inhibitor, in patients with RET fusion-positive early-stage non-small-cell lung cancer who had received curative-intent definitive therapy. Participants were randomized to adjuvant selpercatinib versus placebo for up to 3 years, with investigator-assessed event-free survival as the primary endpoint. If it improves outcomes, adjuvant RET inhibition could reduce recurrence risk in surgically or radiotherapeutically treated RET fusion-positive NSCLC.

Wu YL, Hochmair M, Yang Y et al. · The New England journal of medicine · (2026) · View on PubMed ↗

Perioperative Apalutamide in High-Risk Localized Prostate Cancer.

In a phase 3, double-blind, placebo-controlled trial, perioperative apalutamide was tested in patients with newly diagnosed high-risk localized or locally advanced prostate cancer undergoing radical prostatectomy with pelvic lymph-node dissection. Patients received androgen-deprivation therapy (ADT) plus apalutamide versus ADT plus placebo for six cycles before and after surgery, with dual primary endpoints including a composite of pathological complete response or minimal residual disease. Positive results would support adding apalutamide to perioperative ADT to improve pathologic response and potentially reduce relapse in high-risk localized prostate cancer.

Taplin ME, Gleave M, Shore ND et al. · The New England journal of medicine · (2026) · 1 citations · View on PubMed ↗

Daraxonrasib or Chemotherapy in Previously Treated Metastatic Pancreatic Cancer.

This phase 3, international, open-label randomized trial compared daraxonrasib, an oral RAS(ON) multiselective tri-complex inhibitor targeting active GTP-bound mutant and wild-type RAS, versus investigator’s-choice chemotherapy in previously treated metastatic pancreatic ductal adenocarcinoma. The study’s dual primary endpoints were overall survival and progression-free survival. If daraxonrasib improves survival or disease control, it would represent a new targeted approach for RAS-driven mPDAC after prior therapy.

O’Reilly EM, Wainberg ZA, Hendifar AE et al. · The New England journal of medicine · (2026) · View on PubMed ↗

PARP and Androgen-Signaling Inhibition plus ADT in Metastatic Prostate Cancer.

This ongoing phase 3, double-blind trial evaluated talazoparib (a PARP inhibitor) added to androgen-signaling inhibition plus ADT in metastatic prostate cancer that is androgen pathway modulation-sensitive and harbors homologous recombination repair gene alterations. Patients were randomized to talazoparib versus control within this genetically selected cohort, aiming to determine whether PARP inhibition improves clinical outcomes beyond androgen pathway blockade. Demonstrating benefit would further personalize metastatic prostate cancer treatment by linking PARP inhibitor efficacy to homologous recombination repair defects.

Agarwal N, Matsubara N, Azad AA et al. · The New England journal of medicine · (2026) · 1 citations · View on PubMed ↗

A randomised study of encorafenib, cetuximab, and FOLFIRI versus FOLFIRI with or without bevacizumab in BRAF V600E-mutant colorectal cancer: BREAKWATER Cohort 3.

In the randomized BREAKWATER Cohort 3 trial, previously untreated patients with BRAF V600E-mutant metastatic colorectal cancer were assigned to encorafenib plus cetuximab with FOLFIRI (EC+FOLFIRI) versus FOLFIRI with or without bevacizumab (control). The study found differences in objective response rate and progression-free survival assessed by blinded independent central review (BICR), along with safety outcomes, between the targeted regimen and control strategies. This is clinically significant because it further defines the comparative efficacy and tolerability of BRAF-targeted therapy combinations for BRAF V600E mCRC.

Kopetz S, Tabernero J, Lonardi S et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Monoclonal antibodies targeting inflammatory pathways in COPD - evidence and opportunities.

This narrative review assessed evidence and therapeutic opportunities for monoclonal antibodies targeting inflammatory pathways in chronic obstructive pulmonary disease (COPD). It highlights that, beyond inhaled therapy, multiple immune/inflammatory pathways implicated in COPD exacerbations—particularly neutrophilic inflammation linked to type 1 and type 3 immune responses—may be actionable with monoclonal antibodies (trial specifics are truncated). The significance is to guide future targeted biologic development and patient selection strategies for COPD patients who remain exacerbation-prone despite optimized standard care.

Ross BA, Jeskey J, Couillard S · Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology · (2026) · View on PubMed ↗ · Free PDF ↗

The role of Wnt signalling in the pathogenesis and therapy of age-related macular degeneration (AMD).

This review article examined the role of Wnt signaling—especially the canonical Wnt/β-catenin pathway—in the pathogenesis and potential therapy of age-related macular degeneration (AMD). It frames Wnt signaling as a fundamental pathway involved in processes relevant to retinal/choroidal homeostasis and neovascular AMD, where neovascularization sprouts from the choriocapillaris into the retina (specific therapeutic candidates are truncated). The significance is translational: modulating Wnt/β-catenin signaling is proposed as a potential strategy to slow or prevent AMD progression, particularly neovascular AMD.

Hyttinen JMT, Salminen A, Kauppinen A et al. · Biochemical pharmacology · (2026) · View on PubMed ↗

A Randomized Phase III Trial of Anthracyclines Followed by Taxane versus Taxane Plus Carboplatin as (Neo)Adjuvant Therapy in Patients with Triple-Negative Breast Cancer: KCSG BR 15-1 PEARLY Trial.

This randomized phase III trial in patients with stage II–III triple-negative breast cancer (TNBC) compared standard neoadjuvant/adjuvant doxorubicin plus cyclophosphamide followed by a taxane versus adding carboplatin to the taxane after doxorubicin/cyclophosphamide. The key finding was that carboplatin addition was evaluated for efficacy and safety with the primary endpoint focused on improving response outcomes (e.g., pathologic complete response) relative to taxane-only control. If carboplatin improves (neo)adjuvant efficacy without unacceptable toxicity, it would support platinum-containing standard therapy for early-stage TNBC in both neoadjuvant and adjuvant settings.

Kim GM, Jung KH, Jeung HC et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗

Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in advanced squamous non-small-cell lung cancer (HARMONi-6): interim overall survival analysis of a randomised, double-blind, phase 3 trial in China.

In the HARMONi-6 randomized, double-blind phase III trial in China, first-line advanced squamous non-small-cell lung cancer (NSCLC) patients were assigned to ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy. The key finding reported here was the prespecified interim overall survival analysis comparing these PD-1/VEGF bispecific versus PD-1 monoclonal antibody strategies. Clinically, demonstrating an overall survival advantage would support ivonescimab-based first-line treatment for advanced squamous NSCLC.

Lu S, Liu B, Luo Y et al. · Lancet (London, England) · (2026) · View on PubMed ↗

Real-World Outcomes After Switching to Faricimab in Patients with Chronic Diabetic Macular Edema at a Tertiary Eye Center in Singapore.

This retrospective single-center cohort study evaluated real-world visual and anatomical outcomes in Singaporean patients with diabetic macular edema (DME) who switched to faricimab after suboptimal response to prior anti-VEGF or other therapies. Patients received 3–4 consecutive intravitreal faricimab injections (2022–2024), and the study assessed changes in best available visual acuity (ETDRS letters) and ocular anatomy after the switch. The findings inform how faricimab performs in routine practice for treatment-refractory DME populations.

Fukutsu K, Goh RA, Zheng F et al. · Ophthalmology and therapy · (2026) · View on PubMed ↗ · Free PDF ↗

Amivantamab in recurrent/metastatic HNSCC after checkpoint inhibitor and chemotherapy: pivotal results from the phase 1b/2 OrigAMI-4 study.

This phase 1b/2 OrigAMI-4 study evaluated subcutaneous amivantamab, an EGFR–MET bispecific antibody, in participants with recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC) after PD-(L)1 inhibitor and platinum-based chemotherapy. The pivotal results reported objective response rate (RECIST v1.1) as the primary endpoint, with secondary outcomes including duration of response and progression-free survival. The study supports amivantamab as a targeted option for EGFR/MET-driven R/M HNSCC in the post-checkpoint inhibitor setting.

Burtness B, Rosenberg AJ, Calderon B et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Afatinib Versus Osimertinib for Non-Small Cell Lung Cancer With Uncommon EGFR Mutations: Real-World Outcomes.

This multicenter retrospective cohort study compared first-line afatinib versus osimertinib in advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) with uncommon EGFR mutations (excluding exon 20 insertions and de novo T790M) across 29 Japanese hospitals. Using inverse probability of treatment weighting to balance baseline differences, it assessed real-world outcomes including treatment effectiveness and subsequent therapy patterns. The results help clarify which EGFR TKI strategy may be preferable for uncommon EGFR-mutant NSCLC in routine clinical practice.

Nagano Y, Yokouchi H, Saito R et al. · Cancer science · (2026) · View on PubMed ↗ · Free PDF ↗

Neoadjuvant Sacituzumab Govitecan in Patients With Muscle-Invasive Bladder Cancer: Primary Results of the SURE-01 Trial.

This phase II SURE-01 trial tested neoadjuvant sacituzumab govitecan (SG) followed by radical cystectomy in adults with muscle-invasive bladder cancer (cT2–T4aN0M0) who were ineligible for or refused neoadjuvant chemotherapy. The primary analysis evaluated the neoadjuvant SG regimen’s efficacy (including pathologic response endpoints) and reported primary and biomarker results. The study is clinically significant because it offers a potential chemotherapy-free neoadjuvant option for MIBC patients who cannot receive standard NAC.

Necchi A, de Jong JJ, Maiorano BA et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗ · Free PDF ↗

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Immunotherapy & cancer vaccines (PD-1/TCER/mRNA/combination)

Tumor-targeted interferon-α gene therapy for glioblastoma: a phase 1 trial.

This phase 1/2a first-in-human dose-escalation trial studied Temferon-a, an engineered autologous stem cell transplant delivering interferon-α2 via myeloid progeny, in 24 newly diagnosed glioblastoma patients with an unmethylated MGMT promoter. Interim results show tumor-targeted local interferon-α2 delivery designed to reprogram the myeloid-driven immunosuppressive glioblastoma tumor microenvironment and activate antitumor immunity, with dosing across eight cohorts using 0.5×10^6 to 4.0×10^6 CD34+ cells/kg and different conditioning regimens. If safety and immunologic efficacy are confirmed, this gene-therapy platform could provide a new immunotherapy strategy for immunologically “cold” glioblastoma by leveraging recruited myeloid cells as in situ cytokine factories.

Gentner B, Eoli M, Farina F et al. · Nature medicine · (2026) · View on PubMed ↗

Perioperative serplulimab with neoadjuvant chemotherapy versus perioperative chemotherapy in PD-L1-positive gastric cancer (ASTRUM-006): a randomised, double-blind, multicentre, phase 3 study.

This randomized, double-blind, multicenter phase 3 ASTRUM-006 trial studied perioperative serplulimab (an anti–PD-1/PD-L1 immune checkpoint inhibitor) combined with S-1 plus oxaliplatin (SOX) versus perioperative chemotherapy alone in PD-L1-positive, locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma. The trial evaluated whether adding neoadjuvant serplulimab followed by adjuvant serplulimab improves efficacy and safety in patients with PD-L1 combined positive score (CPS) ≥5. If positive, the results would be clinically significant because they could establish a new standard perioperative chemo-immunotherapy regimen for PD-L1-positive resectable gastric/GEJ cancer.

Shen L, Zhang X, Ji K et al. · Lancet (London, England) · (2026) · View on PubMed ↗

Adjuvant Nivolumab vs Observation in Resected Non-Small Cell Lung Cancer: A Randomized Clinical Trial.

This randomized phase 3 clinical trial studied adjuvant nivolumab versus observation in patients with resected non-small cell lung cancer (NSCLC) with any PD-L1 expression and in a subgroup with at least 50% PD-L1 expression. The abstract indicates the trial was designed to determine whether adjuvant nivolumab improves disease-free survival and overall survival after upfront surgery, with long median follow-up (72.6 months). If positive, the results would establish whether perioperative benefit from nivolumab extends to a post-surgery adjuvant setting across PD-L1 strata.

Chaft JE, Sun Z, Rudin CM et al. · JAMA · (2026) · View on PubMed ↗

Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase 2b KEYNOTE-942 Study.

The randomized phase 2b KEYNOTE-942 study evaluated intismeran autogene (mRNA-4157; individualized neoantigen mRNA) plus pembrolizumab versus pembrolizumab alone in patients with resected stage IIIB–IV cutaneous melanoma. The 5-year update reported recurrence-free survival as the primary endpoint and distant metastasis-free survival and safety as secondary endpoints for the intismeran+PD-1 cohort versus PD-1 monotherapy. If long-term disease control is improved, this would strengthen the clinical role of individualized mRNA neoantigen vaccination combined with PD-1 blockade after resection.

Khattak A, Carlino MS, Meniawy T et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

MAGE-A4/MAGE-A8-targeted TCR-based bispecific T cell engager in recurrent and/or refractory solid tumors: a phase 1 trial.

This phase 1 first-in-human trial evaluated IMA401, a MAGE-A4/MAGE-A8-targeted HLA-A02:01 peptide TCR-based bispecific T cell engager, in 61 patients with recurrent and/or refractory solid tumors, with IMA401 given alone or with pembrolizumab. The key finding from the prespecified interim analysis was the establishment of safety/tolerability and dose-ranging outcomes to support determination of the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) for IMA401 monotherapy and combination therapy. Clinically, targeting MAGE-A4/MAGE-A8 with a TCR-based TCER (IMA401) offers a strategy to enhance tumor-specific T-cell engagement in HLA-A02:01-positive patients.

Wermke M, Ochsenreither S, Jaeger D et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗

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Mechanisms of tumor resistance & microenvironment (omics/modeling)

Deacetylated PCBP1 licenses PARP1 activity for DNA damage repair.

This mechanistic study investigated how the RNA-binding protein PCBP1 regulates PARP1 during the DNA damage response, focusing on post-translational control by the histone deacetylase SIRT7. The key finding was that PCBP1 inhibits PARP1 activity under physiological conditions, and that SIRT7-mediated deacetylation of PCBP1 at K314 and K351 disrupts PCBP1–PARP1 interaction, thereby permitting PARP1 activation early after DNA damage. Scientifically, this identifies a specific PCBP1 acetylation switch controlled by SIRT7 that could be exploited to modulate PARP1-dependent DNA repair and influence DNA damage–targeted therapies.

Shu Y, Zhang J, Zhou L et al. · Molecular cell · (2026) · View on PubMed ↗

A targeted combination therapy achieves effective pancreatic cancer regression and prevents tumor resistance.

The study examined whether genetic ablation of KRAS signaling nodes (RAF1, EGFR, and STAT3) and a targeted drug combination (RMC-6236/daraxonrasib plus afatinib plus SD36) could overcome resistance in orthotopic pancreatic ductal adenocarcinoma (PDAC) driven by Kras/Tp53 mutations. Both the triple genetic ablation and the triple-inhibitor regimen produced complete and permanent regression of orthotopic Kras/Tp53 PDAC and prevented tumor resistance. These findings support a strategy of simultaneously blocking multiple KRAS pathway branches (RAF1, EGFR, STAT3) to achieve durable responses in KRAS-driven PDAC.

Liaki V, Barrambana S, Kostopoulou M et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Which evolutionary game-theoretic model best captures NSCLC dynamics?

The study compared evolutionary game-theoretic mathematical models to identify which best captures NSCLC dynamics using in-vitro data tracking drug-sensitive and drug-resistant cell populations under different conditions. It fit two-population models incorporating growth functions (logistic, Gompertz, von Bertalanffy) and drug-efficacy terms (Norton–Simon, linear, ratio-dependent) using datasets that included treatment with alectinib and the presence or absence of cancer-associated fibroblasts (CAFs). The work provides a modeling framework for predicting how NSCLC populations evolve and respond to targeted therapy in microenvironment-dependent ways.

Garjani H, Dubbeldam J, Staňková K et al. · PloS one · (2026) · View on PubMed ↗

Dynamic genetic and nongenetic RAS pathway activation drives resistance to FLT3 and BCL2 inhibitor therapy.

The study used multiomic single-cell DNA/protein and RNA/protein profiling to characterize how dynamic genetic and nongenetic RAS pathway activation drives resistance during treatment with the FLT3 inhibitor gilteritinib and the BCL2 inhibitor venetoclax in acute myeloid leukemia (AML). In a clinical trial cohort, it showed that relapse involves both genetically distinct clonal evolution and shifts in malignant transcriptional/immunophenotypic states that bulk sequencing alone cannot fully resolve. This supports a resistance mechanism in which RAS pathway reprogramming can be both genetic and state-based, informing combination strategies beyond single-agent mutation targeting.

Kennedy VE, Peretz CAC, Walia A et al. · Blood · (2026) · View on PubMed ↗

Interplay between cohesin and TORC1 links chromosome segregation and gene expression to environmental changes.

This eLife study examined how the TORC1 signaling pathway interacts with the cohesin complex to coordinate chromosome segregation and gene expression in response to environmental changes in fission yeast. Through genetic analysis of TORC1 hypomorphic mutants identified as suppressors of mis4-G1487D defects and mechanistic experiments, the authors showed TORC1 modulates cohesin functions affecting segregation and expression near chromosome ends. These findings connect conserved growth/metabolism signaling (TORC1) to genome organization (cohesin), offering a framework for how cells adapt chromosome behavior under changing conditions.

Besson D, Vaur S, Vazquez S et al. · eLife · (2026) · View on PubMed ↗ · Free PDF ↗

Cancer stem cells synthesize proline to attenuate oxidative stress.

The study investigated how cancer stem cells in glioblastoma regulate amino-acid metabolism, focusing on proline synthesis, and examined the roles of the stem-cell transcription factor SOX2 and the signaling molecule FAM3C. It found that glioblastoma cancer stem cells had increased intracellular proline relative to differentiated progeny via FAM3C-induced expression of proline-synthesis enzymes, which attenuated oxidative stress. This mechanistic link between SOX2–FAM3C signaling and proline metabolism suggests a potential metabolic vulnerability to target cancer stem-cell survival under oxidative stress.

Wu W, Zhang P, Wang D et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗

Aspartate deficiency amplifies cGAS-STING signaling in antitumor immunity.

The study tested whether aspartate metabolism regulates innate immune sensing by modulating cyclic GMP-AMP synthase (cGAS)–STING signaling using pharmacologic screening and aspartate depletion (genetic and aminooxyacetic acid-mediated, AOA-mediated) in antitumor immunity models. It showed that reducing aspartate levels potentiated cGAS–STING signaling, increasing type I interferon and interferon-stimulated gene upregulation, and mechanistically linked this to downstream disruption of de novo pyrimidine synthesis causing mitochondrial DNA (mtDNA) replication stress, mtDNA double-strand breaks, and mtDNA release. These results identify aspartate metabolism as a regulator of cGAS–STING-driven antitumor immunity and suggest metabolic modulation as a strategy to enhance interferon responses.

Liao Y, Wang H, Liu H et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗

PRMT1-Mediated LDHA Methylation Drives STAT3 Lactylation to Orchestrate Intestinal Inflammation and Tumorigenesis.

The study investigated how PRMT1-mediated methylation of LDHA regulates STAT3 lactylation to drive intestinal inflammation and tumorigenesis, using macrophage-dependent mechanisms and genetic ablation of PRMT1 in myeloid cells. It found that SAM promoted STAT3 Y705 phosphorylation and increased IL-10 expression in macrophages, while PRMT1 loss in myeloid cells impaired STAT3 activation and worsened colitis and inflammation-associated tumorigenesis, linking a PRMT1–LDHA lactate axis to STAT3 regulation. These findings identify PRMT1-dependent metabolic-epigenetic signaling as a potential therapeutic target to modulate STAT3-driven intestinal inflammatory and cancer pathways.

Wang H, Zhang M, Gong W et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗

Antiandrogen therapy induces mitochondrial oxidative phosphorylation to promote castration resistance in prostate cancer.

This study examined how antiandrogen therapy drives metabolic remodeling in prostate cancer, focusing on mitochondrial oxidative phosphorylation (OXPHOS) as a driver of castration resistance. It found that prostate cancer cells increase mitochondrial OXPHOS after androgen receptor signaling inhibitor (ARSI) treatment without a significant change in glycolysis, and that this remodeling depends on glucose and glutamine utilization. The significance is mechanistic and therapeutic: targeting mitochondrial OXPHOS may help prevent or overcome ARSI resistance in castration-resistant prostate cancer.

Li K, Luo C, Zhang H et al. · Free radical biology & medicine · (2026) · View on PubMed ↗

Microenvironment T-Type calcium channels regulate neuronal and glial processes in tumor cells to promote glioblastoma growth.

This mechanistic study investigated how microenvironment T-type calcium channels (Cav3, focusing on Cav3.2) regulate neuronal/glial processes that affect glioblastoma (GBM) growth, using Cav3.2 knockout mice and syngeneic GBM grafts. The key finding was that loss of Cav3.2 in the host microenvironment altered neuron–GBM stem cell interactions and reduced GBM growth, supported by electrophysiology, co-culture assays, and single-cell RNA-seq. The significance is that Cav3.2-dependent microenvironment signaling may be a therapeutic target to slow GBM progression.

Dube CJ, Zhang Y, Saha S et al. · Neuro-oncology · (2026) · View on PubMed ↗

Current advances in immunotherapy for KRAS-Mutant pancreatic cancer.

This review examined how KRAS mutations shape the immunosuppressive tumor microenvironment in KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) and thereby affect responses to immunotherapy, including immune checkpoint inhibitors (ICIs). It highlights mechanisms such as immune-cell dysfunction, dense fibrotic stroma, and altered tumor metabolism that collectively create a “cold tumor” phenotype and drive resistance to ICIs. These insights support rational multimodal immunotherapy combinations tailored to KRAS-driven immune evasion in PDAC.

Li M, Wang X, Li P et al. · Clinical and experimental medicine · (2026) · View on PubMed ↗ · Free PDF ↗

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Precision oncology platforms (organoids/PDX/biomarker-guided)

Patient-derived organoids guide personalized therapy for KRAS-mutant pancreatic cancer: synergistic MEK/mTOR inhibition and predictive chemotherapy responses.

The study used patient-derived organoids (PDOs) and patient-derived xenografts (PDXs) from 66 pancreatic ductal adenocarcinoma samples with KRAS mutations to guide personalized therapy, combining next-generation sequencing (NGS) of 425 oncogenes with in vitro drug screening of 32 drugs. It identified synergistic treatment strategies in KRAS-mutant PDOs, including MEK inhibition with trametinib combined with mTOR inhibition (AZD8055) or pan-CDK inhibition (flavopiridol), and linked organoid responses to predictive chemotherapy sensitivity. These results support PDO-guided combination targeting as a practical precision approach for KRAS-mutant PDAC, potentially improving selection of effective drug regimens.

Wang X, Liu L, Li F et al. · Frontiers in immunology · (2026) · View on PubMed ↗ · Free PDF ↗

The role of the 21-gene assay in the neoadjuvant setting for hormone receptor-positive HER2-negative breast cancer: Impact on systemic and surgical treatment decisions.

This review evaluated how the 21-gene assay (Oncotype DX) in the neoadjuvant setting for hormone receptor-positive (HR+) HER2-negative early breast cancer influences systemic therapy and surgical de-escalation decisions. The key finding was that 21-gene assay results can meaningfully affect treatment choices by identifying patients who may be candidates for less intensive systemic therapy and potentially less extensive surgery after downstaging. Clinically, using the assay in neoadjuvant care could help personalize therapy to reduce overtreatment while maintaining oncologic outcomes.

Zotano ÁG, Allweis TM, Foerster R et al. · Cancer treatment reviews · (2026) · View on PubMed ↗ · Free PDF ↗

Impact of Population-Based Pathogenic Variant Testing on Risk-Based Breast Screening Recommendations: A Secondary Analysis of the WISDOM Study.

This secondary analysis of the WISDOM Study cohort evaluated how adding pathogenic variant (PV) testing changes risk-based breast screening recommendations beyond clinical risk factors and polygenic risk. The key finding was that PV carriers would be recommended for high-risk screening at rates that depend on whether clinical risk alone or clinical plus polygenic risk is used for stratification. The significance is that it informs how PV testing should be integrated into population-based risk models to optimize screening recommendations.

Shieh Y, Heise RS, Madlensky L et al. · JAMA oncology · (2026) · View on PubMed ↗

Low-Dose Tamoxifen in Noninvasive Breast Neoplasia: Long-Term Results From an Individual-Participant Data Pooled Analysis.

This individual-participant data pooled analysis assessed long-term outcomes of low-dose tamoxifen in women with estrogen receptor-positive or unknown ductal carcinoma in situ (DCIS), microinvasive carcinoma, or high-risk breast lesions. Participants received low-dose tamoxifen (5 mg daily or 10 mg every other day for 2–5 years) versus control, and the key finding was the durability of breast cancer-free interval benefit over long follow-up with analyses by menopausal status and recurrence site. These results support lower-dose tamoxifen as a potentially less toxic risk-reduction strategy for noninvasive breast neoplasia.

Gandini S, Guerrieri-Gonzaga A, Serrano D et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗

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Oncology supportive/health systems & workforce modeling

Cost-Effectiveness of Fecal Immunochemical Testing Alone vs Co-Testing With Helicobacter pylori Stool Antigen.

This cost-effectiveness analysis modeled lifetime outcomes of population-based gastric cancer screening in Taiwan, comparing biennial fecal immunochemical testing (FIT) alone versus adding a one-time Helicobacter pylori stool antigen test. Using a Markov decision-analytic model informed by a pragmatic randomized trial in Changhua County, it projected long-term health benefits and costs over a 30-year horizon. The results are intended to guide whether adding H. pylori stool antigen testing to FIT screening is economically and clinically worthwhile for gastric cancer prevention.

Lee YC, Liu JH, Mülder DT et al. · JAMA · (2026) · View on PubMed ↗

Quantifying Weight Loss Prior to Pancreatic Cancer Diagnosis: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis quantified weight loss prior to pancreatic cancer diagnosis by searching multiple databases for studies reporting quantitative pre-diagnosis weight loss and BMI change. The key finding is a pooled estimate of the magnitude of weight loss (kg) and BMI change (kg/m²) occurring before diagnosis, derived from meta-analytic synthesis of eligible studies. Clinically, this improves the evidence base for using quantified pre-diagnostic weight loss as a potential diagnostic marker to support earlier detection of pancreatic cancer.

Price CA, Cooke D, Mold F et al. · Cancer medicine · (2026) · View on PubMed ↗ · Free PDF ↗

Cancer workforce-a global crisis: a Lancet Oncology Commission.

This Lancet Oncology Commission modeled the current and future global cancer burden and workforce needs across 17 common cancers and 18 cancer workforce personnel types, with emphasis on disparities between high-income countries and low- and middle-income countries (LMICs). The key finding was that rising cancer incidence is projected to increase workforce demand globally, disproportionately stressing systems in LMICs where trained personnel are most scarce. The work is significant because it provides actionable guidance to strengthen the global cancer workforce to reduce survival disparities.

Hricak H, Ward ZJ, Moraes FY et al. · The Lancet. Oncology · (2026) · 6 citations · View on PubMed ↗

Structured exercise program following adjuvant chemotherapy for colon cancer: A cost-utility analysis of the CHALLENGE trial.

This pre-specified cost-utility analysis evaluated the economic value of a 3-year structured exercise program (SEP) versus health education materials (HEM) in the phase III CHALLENGE trial for stage III or high-risk stage II colon cancer after surgery and adjuvant chemotherapy. Using prospectively collected trial data (n=889) from a Canadian public payer perspective over a 5-year horizon, it mapped SF-36 outcomes to health utilities and estimated cost-effectiveness. The analysis is significant for determining whether the survival benefit of SEP translates into good value for healthcare systems.

Chan KK, Chu RW, Cheung MC et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗ · Free PDF ↗

Disease-modifying treatment preferences and decision-making in a multiple sclerosis randomized and observational clinical trial (DELIVER-MS).

The DELIVER-MS study investigated disease-modifying treatment (DMT) preferences and decision-making in treatment-naïve people with relapsing-remitting multiple sclerosis (RRMS) enrolled in a pragmatic randomized controlled trial (EHT vs escalation, ESC) plus a parallel observational study. It used logistic regression to predict participation in the RCT versus observational cohort and to model choice of early high-efficacy treatment (EHT) versus ESC. The findings are important for understanding real-world adoption of high-efficacy DMT strategies and for interpreting outcomes in pragmatic MS trials.

Tallantyre EC, Planchon SM, Howard H et al. · Multiple sclerosis (Houndmills, Basingstoke, England) · (2026) · View on PubMed ↗

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Surgery/operative risk & perioperative outcomes

Lymph Node Dissection and Postoperative Complications After Lung Cancer Resection.

This retrospective cohort study evaluated whether meeting the guideline-concordant lymph node sampling (LNS) “3+1 rule” (at least 3 N2 mediastinal stations and 1 N1 hilar station) after lung cancer resection is associated with increased postoperative complications. It assessed postoperative outcomes in relation to the extent of LNS performed as adoption of the 3+1 rule increases. The study addresses the clinical tradeoff between oncologic thoroughness of LNS and potential surgical morbidity.

Madeka I, Noueihed K, Woodroof J et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗

Spinal Manipulation and Clinician-Supported Self-Management for Preventing Chronic Low Back Pain Impact: The PACBACK Randomized Clinical Trial.

This 2×2 factorial randomized clinical trial tested whether spinal manipulation and clinician-supported biopsychosocial self-management, compared with medical care, prevents progression to chronic impactful low back pain in adults with acute or subacute low back pain at moderate-to-high risk. The trial was conducted at University of Minnesota and University of Pittsburgh clinics with follow-up through June 2024. The results are intended to determine whether nonpharmacologic, clinician-supported interventions can reduce the transition from acute/subacute LBP to chronic impact.

Bronfort G, Meier EN, Leininger B et al. · JAMA internal medicine · (2026) · View on PubMed ↗

Diaphragmatic Atrophy in Children Undergoing Mechanical Ventilation After Cardiac Surgery.

This prospective cohort study evaluated diaphragmatic atrophy in children undergoing mechanical ventilation after cardiac surgery by performing ultrasound assessments at multiple postoperative time points (pre-op, immediate post-op, late post-op, and before extubation) and measuring diaphragmatic thickness, excursion, and maximum inspiratory pressure. It quantified the frequency and severity of postoperative diaphragmatic atrophy and tracked patients for subsequent diaphragm atrophy outcomes. The findings are clinically significant because they characterize early respiratory muscle injury risk in pediatric cardiac surgery patients and support ultrasound-based monitoring to inform ventilation and rehabilitation strategies.

Lopes CLS, Rezende RQ, Ricachinevsky C et al. · Pediatric pulmonology · (2026) · View on PubMed ↗

Early outcomes of redo-TAVI with the SAPIEN 3 platform: the prospective, multicentre ReTAVI registry.

The prospective, multicentre ReTAVI registry studied 30-day procedural and clinical outcomes of redo transcatheter aortic valve implantation (redo-TAVI) in consecutive patients with failed aortic transcatheter heart valves undergoing redo-TAVI with the balloon-expandable SAPIEN 3 platform. Redo-TAVI with SAPIEN 3 showed acceptable early safety and clinical performance at 30 days in this real-world population of patients requiring valve reintervention. These findings support the feasibility of redo-TAVI using SAPIEN 3 in younger/lower-risk patients who outlive their initial transcatheter valve and may inform procedural planning and risk–benefit discussions.

Tarantini G, Fovino LN, Alvarez Covarrubias HA et al. · EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology · (2026) · View on PubMed ↗ · Free PDF ↗

Complications of PI to PIII hemipelvic resections for intermediate and malignant tumours : a systematic review and meta-analysis.

This systematic review and meta-analysis evaluated complications after PI to PIII hemipelvic resections for intermediate and malignant pelvic tumors across 90 original studies published up to 22 July 2025. It pooled overall complication rates using random-effects meta-analysis and assessed differences in complication rates by factors related to surgery and reconstruction failure (details truncated in the abstract). Clinically, the findings aim to better quantify complication risk for complex pelvic tumor resections and inform surgical planning and reconstruction choices.

Smolle MA, Wenzl FA, Laitinen MK et al. · Bone & joint open · (2026) · View on PubMed ↗ · Free PDF ↗

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Cardiovascular & pulmonary critical care/physiology

Standard-Dose Tenecteplase vs Low-Dose Alteplase for Acute Ischemic Stroke From Large-Vessel Occlusion: A Randomized Clinical Trial.

This investigator-initiated, multicenter randomized clinical trial compared standard-dose tenecteplase (0.25 mg/kg) versus low-dose alteplase (0.6 mg/kg) in patients with acute ischemic stroke from large-vessel occlusion who were scheduled for mechanical thrombectomy. The primary aim was to determine whether tenecteplase achieves a higher rate of recanalization on the initial angiogram than low-dose alteplase. If tenecteplase is superior, it would provide evidence supporting regulatory approval and broader use of tenecteplase dosing strategies in Japan.

Inoue M, Hirano T, Fukuda-Doi M et al. · JAMA neurology · (2026) · View on PubMed ↗

GLI1 activation induced by intermittent hypoxia drives cardiac fibroblast activation via enhanced PKM2-mediated glycolysis.

This study investigated how intermittent hypoxia (a hallmark of obstructive sleep apnea) activates cardiac fibroblasts via GLI1 signaling and PKM2-mediated glycolysis in mouse models. Using single-cell RNA sequencing of heart tissue and genetic models with myofibroblast-specific GLI1 overexpression or knockout, the authors tested whether GLI1 activation is a causal driver of fibroblast activation under intermittent hypoxia. Establishing this GLI1→PKM2 glycolysis mechanism would identify potential molecular targets to prevent or treat hypoxia-associated cardiac fibrosis.

Lv B, Zhou L, Du H et al. · European heart journal · (2026) · View on PubMed ↗

Predictors of severe coronary involvement in children with Kawasaki disease: a single-centre cohort study.

This retrospective single-centre cohort study evaluated predictors of severe coronary involvement in 104 children with Kawasaki disease, using coronary artery Z-scores calculated per standardized equations and classified by 2017 American Heart Association criteria. Severe Kawasaki disease (baseline coronary Z-score ≥5.0) was associated with specific clinical, laboratory, treatment-related, and echocardiographic features identified as significant predictors in the cohort. Clinically, these predictors can help stratify pediatric Kawasaki patients early for risk of major coronary artery disease and guide intensity/timing of monitoring and therapy.

Akay N, Torunoglu Z, Aslan E et al. · Cardiology in the young · (2026) · View on PubMed ↗

Autoantibodies in Patients With Arrhythmogenic Cardiomyopathy Activate GSK-3β, Resulting in a Loss of Cardiomyocyte Cohesion.

This study examined how IgG autoantibodies against intercalated disc proteins, including desmoglein-2 (DSG2), from patients with arrhythmogenic cardiomyopathy (ACM), healthy relatives, and murine ACM models affect cardiomyocyte cohesion and signaling. The authors found that these autoantibodies activate GSK-3β, leading to loss of cardiomyocyte cohesion through disruption of intercalated disc integrity. These mechanistic data support an autoimmune contribution to ACM pathogenesis and suggest that targeting GSK-3β or antibody-mediated ICD disruption could be a therapeutic strategy.

Pathak S, Stangner K, Kempf E et al. · Acta physiologica (Oxford, England) · (2026) · View on PubMed ↗ · Free PDF ↗

Electrical impedance tomography-derived flow index during spontaneous breathing trial stratifies the risk of reintubation within 48 h after extubation.

This study evaluated whether an electrical impedance tomography (EIT)-derived flow index (EFI) measured during a spontaneous breathing trial (SBT) predicts early post-extubation failure, specifically reintubation within 48 hours, in mechanically ventilated patients. The key finding was that the EIT-derived EFI during SBT stratified risk of reintubation within 48 hours among patients who completed SBT. Clinically, EFI could provide a noninvasive, bedside physiological marker to identify patients at high risk for early extubation failure and guide weaning decisions.

Zhang R, Xu J, Wu J et al. · Critical care (London, England) · (2026) · View on PubMed ↗ · Free PDF ↗

Vertebral endplate bone marrow lesion composition: relation to Modic change classification and associations with chronic low back pain.

This single-center prospective longitudinal observational cohort study investigated vertebral endplate bone marrow lesion composition (“Modic changes,” MC) using water-fat MRI to develop a quantitative imaging biomarker and relate it to chronic low back pain outcomes. It tested associations between MC compositional measures, conventional MC subtype classification, patient-reported outcomes, and longitudinal conversion between MC types (numerical results are truncated). The scientific significance is improving imaging-based phenotyping of MC to better identify which patients’ lesions are linked to symptoms and progression.

Bonnheim NB, Brumm Z, Link TM et al. · The spine journal : official journal of the North American Spine Society · (2026) · View on PubMed ↗ · Free PDF ↗

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Infectious disease therapeutics & vaccines (real-world/clinical)

Building resilient and response-ready influenza vaccination programs for pandemic preparedness: a comparative analysis from five middle-income countries.

This comparative case study analyzed determinants of resilient and response-ready seasonal influenza vaccination programs in five middle-income countries (MICs). The key finding was that program resilience and pandemic readiness were driven by structural and programmatic elements that varied across countries, rather than by a single uniform factor. Scientifically and for health policy, the cross-country synthesis identifies actionable levers that can strengthen influenza vaccination systems for pandemic preparedness in MIC settings.

Malchione M, Sommers T, Dockery M et al. · BMC health services research · (2026) · View on PubMed ↗ · Free PDF ↗

The Association Between MOG-IgG Positivity and mRNA SARS-CoV-2 Vaccination in Denmark: A Self-Controlled Case Series Study.

This Danish self-controlled case series used nationwide health registers to examine whether MOG-IgG positivity (as a proxy for MOG antibody-associated disease, MOGAD) is associated with mRNA SARS-CoV-2 vaccination among Danish residents who had their first positive MOG-IgG test between 1 Nov 2020 and 31 Dec 2023. The abstract indicates an analysis of the temporal association between vaccination and subsequent MOG-IgG positivity, but the specific effect estimates are truncated. The study is significant for pharmacovigilance and for clarifying whether mRNA vaccination increases short-term risk of MOGAD in the general Danish population.

Kopp TI, Andreasen AK, Papp V et al. · Pharmacoepidemiology and drug safety · (2026) · View on PubMed ↗ · Free PDF ↗

A Pragmatic Randomized Trial to Evaluate the Vaccine Effectiveness of Bivalent RSV prefusion F Vaccine for Preventing RSV Hospitalizations in Adults (DAN-RSV): Trial Design Update.

This article updates the design of the pragmatic randomized DAN-RSV trial evaluating bivalent RSV prefusion F (RSVpreF) vaccine effectiveness against RSV hospitalizations in adults. It describes enrollment during 2024/2025 and 2025/2026 Northern hemisphere winter seasons, including Danish adults ≥60 years and additional adults ≥18 years in Denmark and Galicia, Spain, using registries and electronic messaging for recruitment (primary endpoints and statistical details are truncated). The clinical significance is to generate real-world evidence on RSV vaccine effectiveness in older and comorbid adult populations.

Lassen MCH, Christensen SH, Johansen ND et al. · American heart journal · (2026) · View on PubMed ↗ · Free PDF ↗

First reported case of Andes hantavirus cardiopulmonary syndrome treated with a combination of favipiravir, ribavirin, icatibant and baricitinib.

This case report described the first documented Andes virus (ANDV) hantavirus cardiopulmonary syndrome (HCPS) case in Spain and the first worldwide use of a combination regimen including favipiravir, ribavirin, icatibant, and baricitinib. A 69-year-old man diagnosed by RT-PCR and serology while asymptomatic received the two antivirals plus two host-directed drugs under compassionate-use authorization in a high-level isolation unit (treatment course/outcomes are truncated). The significance is clinical: it provides early evidence for a potential multi-target therapeutic strategy in severe ANDV HCPS, informing future case series and trials.

Miriam E, Sacristán S, Tatiana MF et al. · Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · (2026) · View on PubMed ↗

Harpagide alleviates sepsis-induced acute respiratory distress syndrome via gut microbiota modulation.

This preclinical study tested whether harpagide (HPG), an iridoid glycoside from Scrophularia ningpoensis, protects against sepsis-induced acute respiratory distress syndrome (ARDS) through gut microbiota modulation using the cecal ligation and puncture (CLP) mouse model. The key finding was that HPG alleviated sepsis-induced ARDS and that the protective effect depended on gut microbiota (assessed using antibiotic depletion and fecal microbiota approaches). Scientifically, it supports a gut-lung axis mechanism and identifies harpagide as a candidate microbiota-targeting therapy for sepsis-associated ARDS.

Sun Y, Xie D, Fu H et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗

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Neuroimmunology & neurodegeneration (biomarkers/pathology/therapeutics)

Dual epitope anti-LILRB4 synthetic T-cell receptor and antigen receptor (STAR)-T-cell therapy for relapsed/refractory acute myeloid leukemia.

This study developed dual epitope anti-LILRB4 STAR-T cell therapy for relapsed/refractory acute myeloid leukemia (AML) by targeting LILRB4, an immunosuppressive receptor highly expressed on monocytic AML blasts but not on hematopoietic stem cells. Using phage display library screening, the authors identified two high-affinity LILRB4 nanobodies and constructed nanobody-based dual epitope anti-LILRB4 STAR-T cells that showed more potent tumor inhibition than comparator constructs in vitro and in vivo. Clinically, this supports LILRB4 as a promising AML-specific target and provides a rationale for STAR-T approaches to overcome antigen-selection limitations in CAR-T for AML.

Lv M, Zheng H, Pei X et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗

miR-146a is a pleiotropic regulator of motor neuron degeneration.

The study profiled microRNAs in motor neurons during degeneration in vivo in amyotrophic lateral sclerosis (ALS) and tested the role of miR-146a using genetic deletion in SOD1G93A mice. miR-146a was downregulated in diseased motor neurons, and miR-146a knockout significantly extended survival in SOD1G93A mice (with the largest benefit in heterozygotes) while reducing spinal cord gliosis without preventing motor neuron loss. This identifies miR-146a as a pleiotropic regulator of ALS motor neuron degeneration and a potential therapeutic target to modulate neuroinflammation.

Galloway DA, Patterson HL, Hoye ML et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗

Multimodal analysis of cell-free DNA identifies epigenetic biomarkers for amyotrophic lateral sclerosis diagnosis and progression.

The study analyzed circulating cell-free DNA (cfDNA) methylation patterns in blood from patients with sporadic ALS, C9orf72-associated ALS, asymptomatic C9orf72 repeat-expansion carriers, and nondisease controls using targeted enzymatic methyl-sequencing (EM-seq) of ~4 million CpG sites. It identified numerous differentially methylated genes, including ALS-relevant risk/pathogenesis genes, and reported that integrating multiple epigenetic features enabled detection of ALS diagnosis and progression. These findings support cfDNA methylation multimodal biomarkers as a minimally invasive liquid-biopsy approach for stratifying ALS and monitoring disease course, including in C9orf72 mutation carriers.

Michels S, Chen C, Ruf WP et al. · The Journal of clinical investigation · (2026) · View on PubMed ↗ · Free PDF ↗

Celiac disease as a model of gut-brain autoimmunity: from gluten exposure to neuropsychiatric manifestations.

This narrative review synthesized evidence on celiac disease (CeD) as a gut-brain autoimmunity model, focusing on neuropsychiatric manifestations across pediatric and adult populations and discussing proposed mechanisms from gluten exposure to brain symptoms. It concluded that CeD is associated with a broad spectrum of neurological and psychiatric outcomes and that multiple immunologic and mechanistic pathways have been proposed, with clinical relevance varying by age group. The review supports CeD screening and tailored therapeutic considerations for neuropsychiatric symptoms and highlights mechanistic gaps for future research.

Pucinischi V, Piersanti M, Di Nardo G et al. · Frontiers in pediatrics · (2026) · View on PubMed ↗ · Free PDF ↗

Complement C5 inhibitors as add-on rescue treatment in severe AQP4-antibody neuromyelitis optica spectrum disorder attacks: a case series and literature review.

The case series and literature review evaluated complement C5 inhibitors as add-on rescue therapy in severe aquaporin-4 antibody neuromyelitis optica spectrum disorder (AQP4-Ab NMOSD) attacks refractory to intravenous methylprednisolone and therapeutic plasma exchange (PLEX) in three patients. It reported clinical use of C5 blockade in patients with severe optic neuritis who did not respond to standard first-line therapies, aiming to rapidly inhibit the terminal complement cascade and prevent downstream astrocytic injury. This suggests C5 inhibitors may be a promising rescue option for steroid/PLEX-refractory AQP4-Ab NMOSD relapses, warranting further controlled studies.

Gan KX, Abu Hassan SHB, Tan XL et al. · Therapeutic advances in neurological disorders · (2026) · View on PubMed ↗ · Free PDF ↗

Anti-inflammatory effects of GLP1-RA drugs.

This review summarized evidence for direct anti-inflammatory effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) across preclinical models and human data in conditions characterized by chronic inflammation. The key finding is that GLP-1 RAs can modulate inflammatory pathways and immune responses beyond glycemic and weight effects, with anti-inflammatory activity reported across multiple organ systems. Scientifically and clinically, this supports exploring GLP-1 RAs as potential anti-inflammatory therapies for diseases where inflammation drives pathology, including diabetes and cardiovascular disease.

Quintana L, Tabaza N, Kurt B et al. · The Journal of clinical endocrinology and metabolism · (2026) · View on PubMed ↗

Syndrome-specific vulnerability of neuronal and glial 4-repeat frontotemporal lobar degeneration-tau.

This neuropathology study investigated syndrome-specific vulnerability of neuronal and glial 4-repeat (4R) tau in frontotemporal lobar degeneration by comparing neocortical and hippocampal distributions of tau inclusions in corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) underlying clinical syndromes such as primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD). The key finding was that the spatial distribution of neuronal and glial tau inclusions differed in a way that aligned with the clinical syndrome, indicating clinicopathologic concordance driven by syndrome-specific vulnerability. These results improve understanding of how 4R tau pathology maps to distinct clinical phenotypes, which can refine diagnosis and inform targeted research into disease mechanisms.

Minogue G, Zouridakis A, Nelson C et al. · Brain : a journal of neurology · (2026) · View on PubMed ↗

American Thyroid Association 2026 Guidelines for Thyroid Disease in Preconception, Pregnancy, and Postpartum.

The American Thyroid Association (ATA) 2026 guidelines synthesized new evidence to address clinical questions in women with thyroid disease across preconception, pregnancy, and postpartum. The key output is updated, evidence-based recommendations for screening, monitoring, and treatment decisions during these reproductive periods. This is significant because it standardizes care to reduce maternal and fetal risks associated with thyroid dysfunction and thyroid autoimmunity.

Korevaar TIM, Leung AM, Alexander EK et al. · Thyroid : official journal of the American Thyroid Association · (2026) · View on PubMed ↗

An Update on Somatic Treatments for Suicide Risk.

This scoping review evaluated pharmacologic and neuromodulatory interventions with potential antisuicidal effects across major psychiatric disorders, synthesizing evidence from randomized controlled trials, meta-analyses, registries, and large cohort/pharmacoepidemiologic studies. The key finding is that multiple treatment classes show associations with reduced suicide risk, and the review distinguishes effects on suicide diathesis from those mediated by improvement in underlying psychiatric symptoms when evidence allows. Scientifically and clinically, it helps prioritize candidate interventions for suicide prevention and identifies gaps where causal evidence remains limited.

Rizk MM, Mann JJ · The American journal of psychiatry · (2026) · 1 citations · View on PubMed ↗

CKLF-like MARVEL transmembrane domain-containing superfamily 8 (CMTM8) promotes Notch signalling to maintain CD8+ T cell- and NK cell-dependent tumour immune escape.

This study examined how CKLF-like MARVEL transmembrane domain-containing superfamily 8 (CMTM8) regulates tumor immune escape by promoting Notch signalling in the tumor microenvironment. Using lentiviral CMTM8 functional editing, subcutaneous xenograft mouse models, and AAV-based shRNA targeting, the authors found that CMTM8 supports immune evasion by affecting CD8+ T cell- and NK cell-dependent antitumor responses, with high CMTM8 expression linked to poorer outcomes in melanoma and colorectal cancer clinical datasets. These findings are significant because they identify the CMTM8–Notch axis as a potential therapeutic target to enhance antitumor immunity.

Li F, Gu L, Chen R et al. · British journal of pharmacology · (2026) · View on PubMed ↗

Peroxisomal DBP deficiency causes male infertility through disruption of lipid homeostasis in Drosophila.

This study used a Drosophila model of peroxisomal D-bifunctional protein (DBP) deficiency (the ortholog of human HSD17B4) combined with single-cell RNA sequencing (scRNA-seq) to determine how peroxisomal β-oxidation disruption causes male infertility. The key finding was that DBP deficiency disrupts lipid homeostasis and alters cellular transcriptional programs in ways consistent with impaired reproductive function. These results provide mechanistic insight into HSD17B4/DBP-related infertility and highlight lipid metabolic dysregulation as a causal pathway.

Wang J, Ma Y, Wang Y et al. · Cellular and molecular life sciences : CMLS · (2026) · View on PubMed ↗ · Free PDF ↗

Learning immunology from mothers and babies.

This review article synthesized current understanding of maternal–fetal immunology, focusing on how pregnancy enables tolerance between genetically discordant maternal and fetal tissues. It emphasizes shared immunity across the maternal–fetal dyad, including microchimerism after parturition and the role of vertically transferred maternal IgG antibodies, while addressing why maternal rejection of fetal tissue and fetal rejection of maternal tissue do not occur. The significance is translational: these mechanisms may inspire new therapeutic strategies for immune tolerance and treatment of common immune-mediated diseases.

Turner LH, Sun J, Brady AE et al. · Mucosal immunology · (2026) · View on PubMed ↗

AI-Driven discovery of brain-penetrant mTOR-independent autophagy enhancers for Alzheimer’s disease.

This AI-driven study (DeepDrugDiscovery) searched for brain-penetrant autophagy enhancers for Alzheimer’s disease that act independently of the mTOR pathway. The key finding is the identification/discovery of candidate compounds predicted to enhance autophagy via an mTOR-independent mechanism while improving blood–brain barrier (BBB) penetration relative to typical mTOR-dependent inducers. This provides a mechanism-centric pipeline for generating more CNS-viable autophagy-targeting therapeutics for Alzheimer’s disease.

Dong Y, Xiao X, Zhuang XX et al. · Autophagy · (2026) · View on PubMed ↗ · Free PDF ↗

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Generated automatically on June 02, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.