PubMed Trending Research Digest — June 03, 2026
A curated digest of 95 trending PubMed articles, automatically categorised and summarised across 15 research areas.
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PubMed Trending Research Digest — June 03, 2026
Automated digest · 95 articles · 15 research areas · June 03, 2026
Overview
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Digital health & palliative care delivery
Time-restricted feeding extends healthspan in both sexes and lifespan in male C57BL/6 J mice.
This study tested whether time-restricted feeding (TRF) with 12-hour or 8-hour nightly feeding windows improves healthspan and lifespan in 264 male and 264 female C57BL/6J mice fed regular chow. TRF improved multiple health measures (including behavioral rhythmicity, body weight/composition, frailty, and disease onset), with the 8-hour TRF group showing the strongest effects and evidence of voluntary caloric restriction. These findings support circadian-aligned TRF as a non-obesity-promoting dietary strategy that can extend healthspan and potentially lifespan, informing translational approaches for metabolic and aging interventions.
Iiams SE, Skinner NJ, Wight-Carter M et al. · Nature aging · (2026) · View on PubMed ↗
Nucleophagy removes cytotoxic trapped PARP1.
This study investigated how PARP inhibitors (PARPi) that trap PARP1 on chromatin are cleared in cells, focusing on the nucleophagy pathway mediated by the selective autophagy receptor TEX264 and the segregase p97/VCP. The authors found that trapped PARP1 is removed via nucleophagy orchestrated by TEX264 and p97/VCP, clarifying a mechanism that can modulate PARPi cytotoxicity. Scientifically, this identifies a specific clearance route for PARP1–chromatin complexes that could be targeted to influence resistance or sensitivity to PARPi in homologous recombination repair–deficient cancers.
Hoslett G, Tribble S, Lascaux P et al. · Nature cell biology · (2026) · View on PubMed ↗
Hallmarks and correlates of effective adoptive cell immunotherapy for cancer.
This review synthesized evidence on adoptive cell immunotherapy (ACT) strategies for cancer, including neoantigen-specific T cells such as tumor-infiltrating lymphocytes (TILs) and TCR-engineered T cells (TCR-T), and discussed immunogenomic and systems immunology correlates of response. It highlights that ACT can produce tumor regression across multiple metastatic solid tumors (e.g., melanoma, breast, and gastrointestinal cancers) when neoantigen targeting and patient-specific immune features align. Clinically, the work frames how immunogenomics and systems-level biomarkers can guide selection and optimization of ACT to improve outcomes in otherwise recalcitrant solid epithelial tumors.
Krishna S, Robbins PF, Lowery FJ et al. · Nature reviews. Immunology · (2026) · View on PubMed ↗
Integrative analyses elucidate transcriptional regulatory functions of risk alleles for metabolic liver disease.
This study mapped how noncoding risk variants for metabolic dysfunction–associated steatotic liver disease (MASLD) regulate transcription in human liver, using chromatin accessibility profiling in MASLD liver nuclei and a massively parallel reporter assay to test variant activity. Risk variants were enriched in cell-type-specific regulatory elements bound by lineage-determining transcription factors, and the reporter assay identified hundreds of differential activity variants (DAVs) whose regulatory effects were cell-type- and stimulus-dependent and perturbed liver-pathology transcriptional networks. These integrative functional genomics results connect MASLD GWAS loci to specific regulatory mechanisms, supporting more precise identification of causal variants and therapeutic targets.
Zhu B, He N, Xiao Y et al. · Nature genetics · (2026) · View on PubMed ↗
Anti-asthma drug montelukast induces autistic behaviors via disrupting neuronal retinoic acid signaling.
This study examined whether montelukast (MTK), a cysteinyl leukotriene receptor antagonist, disrupts neuronal retinoic acid (RA) signaling and induces autistic-like behaviors in rat prefrontal cortex neurons and in wild-type rats. Prenatal or early postnatal MTK exposure disrupted neuronal RA signaling and synaptic plasticity and produced autistic-like behaviors, which were reported to be alleviated by intervention targeting the disrupted pathway. The findings raise a mechanistic safety concern for a widely used anti-asthma drug by linking MTK exposure to altered RA-dependent neurodevelopmental processes relevant to ASD risk.
Hao ZJ, Wu QH, Li YL et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗
Final outcomes of the SOFT and TEXT phase III trials in premenopausal hormone receptor-positive early breast cancer.
This report provides final 15-year outcomes from the SOFT and TEXT phase III trials in premenopausal hormone receptor-positive early breast cancer, comparing tamoxifen (T) versus ovarian function suppression (OFS) plus tamoxifen (T+OFS) versus exemestane (E)+OFS. Across 3047 patients in SOFT and 2660 in TEXT (intention-to-treat), the long-term analysis supports that E+OFS reduces distant recurrence compared with T+OFS. Clinically, these mature results strengthen the evidence base for selecting endocrine regimens in premenopausal patients to improve durable metastatic outcomes.
Francis PA, Pagani O, Fleming GF et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗
Global burden of enteric infectious diseases, diarrhoeal diseases, and corresponding aetiologies, 1990-2023: a systematic analysis for the Global Burden of Disease Study 2023.
This systematic analysis quantified the global burden of enteric infectious diseases and diarrhoeal diseases and attributed causes from 1990–2023 using the Global Burden of Disease Study 2023 framework. It provides updated epidemiological estimates and assesses progress toward the Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) mortality target. The results are significant for public health planning because they identify where disease burden and etiologies are changing, guiding targeted prevention and control strategies.
The Lancet. Infectious diseases · (2026) · View on PubMed ↗
Explosive cytotoxicity of ruptoblasts bridges hormone surveillance and immune defense.
This study identified and characterized “ruptoblasts,” a cytotoxic glandular cell type in regenerative planarian flatworms, and investigated how activin triggers their explosive cell death (“ruptosis”). Ruptosis was induced by activin via activin-driven protein injection, genetic chimerism, or bacterial infection, leading to rapid discharge of diffusible cytotoxic agents that eliminated nearby cells, bacteria, and even mammalian cells within minutes. Scientifically, the work links hormone-based surveillance (activin) to an immune-defense-like cytotoxic mechanism, suggesting a conserved logic for rapid, hormone-triggered innate defense.
Chai C, Sultan E, Sarkar SR et al. · Cell · (2026) · View on PubMed ↗
Reductive death is averted by a conserved de novo lipogenic switch.
This study examined how biguanides (including metformin) can cause toxicity when de novo lipogenesis is impaired, focusing on a conserved de novo lipogenic switch that prevents “reductive death.” The authors showed that biguanide treatment under impaired lipogenesis drives NADPH toxicity, causing catastrophic elevation of NADH/GSH reducing equivalents and accelerated death across models. These findings are significant because they provide a mechanistic explanation for biguanide-associated toxicity risk and identify lipogenesis-dependent protection as a potential determinant of safety and efficacy.
Ahsan FM, Rotti JF, Yerevanian AI et al. · Molecular cell · (2026) · View on PubMed ↗
Proteomic signatures of early retinal neurodegeneration in type 2 diabetes mellitus.
This multi-cohort prospective observational study aimed to identify circulating plasma protein signatures of diabetic retinal neurodegeneration (DRN) and build a clinically usable risk prediction system, integrating high-throughput plasma proteomics with longitudinal optical coherence tomography (OCT). Across a discovery cohort of 1,492 participants (with additional independent validation cohorts), the authors reported protein markers that tracked DRN progression and enabled individualized risk prediction. Clinically, this supports the development of blood-based biomarkers to detect and stratify patients at risk for early retinal neurodegeneration in type 2 diabetes, potentially enabling earlier intervention.
Li H, Zhu Z, Yang S et al. · PLoS medicine · (2026) · View on PubMed ↗
Combined MEK1/2 and Autophagy Inhibition Suppresses Tumor Growth via STING-Mediated Type I Interferon Response in iCCA.
This study examined whether combined MEK1/2 inhibition and autophagy inhibition suppresses tumor growth in intrahepatic cholangiocarcinoma (iCCA) by modulating the STING pathway. The authors found that MEK inhibition activates LKB1–ULK1-dependent autophagy (including PINK1/Parkin-mediated mitophagy) and increases ROS, which in turn limits cGAS–STING–TBK1 type I interferon signaling, and that adding autophagy inhibition restores STING-mediated anti-tumor activity and suppresses growth. These results support a therapeutic strategy of pairing MEK inhibitors with autophagy blockade to enhance innate immune activation in iCCA.
Sun C, Gao Z, Dong E et al. · Cancer science · (2026) · View on PubMed ↗ · Free PDF ↗
Tumor-targeted interferon-α gene therapy for glioblastoma: a phase 1 trial.
This first-in-human phase 1/2a dose-escalation trial studied Temferon-a, a genetically engineered autologous stem cell transplant designed to deliver interferon-α2 via myeloid progeny in 24 newly diagnosed glioblastoma patients with unmethylated MGMT promoter. The interim analysis evaluated Temferon-a doses (0.5×10^6 to 4.0×10^6 CD34+ cells/kg) after surgical resection and radiotherapy to locally activate antitumor immunity in an immunologically “cold” GBM microenvironment. The trial is significant because it tests a tumor-targeted, gene-based immunotherapy strategy aimed at overcoming myeloid-driven immunosuppression in GBM.
Gentner B, Eoli M, Farina F et al. · Nature medicine · (2026) · View on PubMed ↗
Savolitinib in MET-amplified gastric or gastroesophageal junction adenocarcinoma: a phase 2 trial.
This phase 2 open-label multicenter trial evaluated savolitinib, an oral MET inhibitor, in patients with MET-amplified gastric or gastroesophageal junction (G/GEJ) adenocarcinoma who progressed after prior therapy. The study enrolled METamp tumors defined by gene copy number thresholds (including ≥10 for the pivotal phase) and assessed clinical outcomes in an exploratory and pivotal design. The results are clinically significant because they address an unmet need for targeted therapy in METamp G/GEJ cancer where evidence for MET inhibitors has been limited.
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 tested ABBV-706, a SEZ6-targeting antibody-drug conjugate linked to a topoisomerase-1 inhibitor (Top1i), in 288 patients with advanced solid tumors including 124 with relapsed/refractory small cell lung cancer (SCLC). The study evaluated safety, tolerability, and dose-escalation/optimization with expansion cohorts including central nervous system tumors and high-grade neuroendocrine neoplasms. The trial is significant because it explores a SEZ6-directed ADC mechanism for treating SCLC and related neuroendocrine malignancies with a defined molecular target.
Byers LA, Cho BC, Cooper AJ et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗
TP53 deficiency in AML induces resistance to T-cell engagers through an immunosuppressive secretome.
This mechanistic study investigated how TP53 deficiency in acute myeloid leukemia (AML) induces resistance to T-cell engagers by creating an immunosuppressive secretome. Using TP53-deleted primary AML cells and TP53-knockdown AML cell lines in co-culture with T cells stimulated by the BiTE molecule AMG 330 (CD3×CD33), the authors found reduced cytotoxicity and impaired T-cell proliferation/proinflammatory cytokine responses. The findings are significant because they identify TP53 status as a potential resistance determinant for T-cell engager therapies in AML and suggest targets to overcome immunosuppressive microenvironment effects.
Winter L, Pawlowsky L, Muth A et al. · Leukemia · (2026) · View on PubMed ↗ · Free PDF ↗
CBX4 enhances acute monocytic leukemia development via HDAC-mediated suppression of Runx1.
This work investigated the role of chromobox protein homolog 4 (CBX4), a PRC1 component, in acute monocytic leukemia (AML-M5) development and its mechanism of action on RUNX1. CBX4 was elevated in peripheral blood from AML-M5 patients, and in zebrafish models CBX4 overexpression promoted AML-M5–like disease by suppressing Runx1 via HDAC-mediated repression. The study links CBX4–HDAC–RUNX1 signaling to AML-M5 pathogenesis, supporting CBX4/HDAC/RUNX1 as potential mechanistic targets for therapy.
Ye Y, Zhang Y, Wang T et al. · Communications biology · (2026) · View on PubMed ↗ · Free PDF ↗
Selection of human hematopoietic stem cells bearing the intended functional edit by transient AND-gate reporters.
The study developed and tested a selection strategy for human hematopoietic stem/progenitor cells (HSPCs) using transient AND-gate reporters to enrich for cells with intended functional genome edits. Using the SMArT (selection by means of artificial transactivators) approach, HDR-edited HSPCs were enriched to 80–100% purity while cells with undesired on-target edits were preferentially depleted. This improves the efficiency and safety of targeted gene-sized cassette integration in HSPCs, advancing clinical-grade genome editing for genetic disease treatment.
Canarutto D, Fiumara M, Venkatesan V et al. · Nature biotechnology · (2026) · View on PubMed ↗ · Free PDF ↗
Decoding the origins of cellular self-organization for engineered biology.
This Perspective article analyzed how physical constraints and iterative rule-based interactions drive cellular self-organization relevant to engineered biology, drawing on stem-cell models of embryogenesis and organogenesis. It argues that constraints such as oxygen and nutrient transport lead to predictable collective behaviors (e.g., cavitation, folding, branching) that couple mechanics, signaling, and gene regulation to produce tissue-scale spatiotemporal patterning. The synthesis highlights actionable design principles and failure modes for engineering tissues and organs using stem-cell and developmental systems.
Chen Q, Zernicka-Goetz M · Nature biotechnology · (2026) · View on PubMed ↗
Generation of membrane-permeable cyclic peptides inhibiting protein-protein interaction.
The study aimed to generate membrane-permeable cyclic peptides that inhibit protein–protein interactions (PPIs) without prior lead structures, focusing on E3 ligase adaptor Keap1 and its substrate Nrf2. By functionally screening a nanomole-scale library of 15,360 fully random cyclic peptides, the authors identified sub-kDa cyclic peptide inhibitors of the Keap1–Nrf2 PPI and then performed optimization (details truncated in the abstract). This provides a generalizable route to drug-like, cell-penetrant cyclic peptide PPI inhibitors for targets previously considered undruggable.
Ji X, Farrera-Soler L, Li J et al. · Nature chemical biology · (2026) · View on PubMed ↗
Passive heart-rate monitoring during smartphone use in everyday life.
This study evaluated passive heart-rate monitoring (PHRM) using deep learning from facial video-based photoplethysmography during everyday smartphone use in 485 participants for development and 211 participants for validation. PHRM estimated heart rate and resting heart rate (RHR) in laboratory and free-living settings and outperformed state-of-the-art methods (specific metrics truncated in the abstract). The large-scale validation supports smartphone-based, wearable-free cardiovascular monitoring as a practical tool for longitudinal health assessment.
Liao S, Di Achille P, Wu J et al. · Nature · (2026) · View on PubMed ↗ · Free PDF ↗
Deep brain stimulation induces white matter remodeling and functional changes to brain-wide networks.
The study investigated how deep brain stimulation (DBS) remodels white matter and alters brain-wide networks by targeting white matter adjacent to the subcallosal anterior cingulate cortex in macaques. SCC-DBS selectively increased fractional anisotropy in the cingulum bundle and, at the cellular level, increased myelinated oligodendrocytes and the degree of myelination in the mid-cingulum bundle, alongside network changes (truncated). These mechanistic findings link DBS to microstructural myelin remodeling, informing how DBS exerts therapeutic effects in treatment-resistant neuropsychiatric disorders.
Fujimoto SH, Fujimoto A, Elorette C et al. · Nature neuroscience · (2026) · View on PubMed ↗
Engineered Bacteroides thetaiotaomicron sense gut inflammation and deliver therapeutic molecules to alleviate colitis in mice.
This study engineered the human gut commensal Bacteroides thetaiotaomicron to sense intestinal inflammation biomarkers and deliver therapeutic molecules to alleviate colitis in mice. The authors created chromosomally integrated genetic circuits in Bacteroides (Btbots) that detect deoxycholic acid (DCA) and nitric oxide (NO) and enhance therapeutic delivery/anti-inflammatory activity (details truncated). The work demonstrates a programmable, colonizing therapeutic microbe platform that couples biomarker sensing with targeted delivery for inflammatory bowel disease treatment.
Ye M, Liu X, Peng Z et al. · Nature microbiology · (2026) · View on PubMed ↗
Segmental specification of the human female fetal reproductive tract revealed by spatiotemporal dynamics.
The study mapped spatiotemporal development of the human female reproductive tract (FRT) to determine how segmental specialization emerges during gestation. Using a gestational week 10–25 spatiotemporal transcriptomic atlas, it found that upper versus lower FRT segments contain distinct mesenchymal and epithelial cell subpopulations beginning as early as GW10, with segment-specific lineage origins (details truncated). This provides a developmental framework for understanding congenital reproductive tract anomalies and adult reproductive disorders linked to segmental mispatterning.
He Z, Wang Q, Ding L et al. · Nature cell biology · (2026) · View on PubMed ↗
Developmental chronology of mouse embryo from 2-cell stage through birth.
This study generated the mouse developmental Cell and Lineage Atlas (mdCLA) to improve temporal resolution of single-cell embryo atlases from the 2-cell stage through birth. mdCLA profiled 37 time points (E1.5 to E19.0) with ~2 million cells and ~4,500 genes detected per cell, enabling identification of organ-specific cell types and revealing divergent gene expression programs between early and late-stage metanephric progenitors (details truncated). The atlas provides a high-resolution resource for dissecting developmental timing and lineage dynamics underlying organogenesis.
Cao S, Lin L, Feng H et al. · Nature cell biology · (2026) · View on PubMed ↗
Population-specific heterogeneity in ontogeny of the broadly-conserved blood transcriptional program during the first week of life.
This study analyzed day-of-life effects on blood gene expression and cell-type composition during the first week of life in two neonatal populations from The Gambia and Papua New Guinea using block randomization to reduce batch effects. It found population-specific heterogeneity in the ontogeny of a broadly conserved blood transcriptional program, indicating that conserved immune-development trajectories diverge mechanistically across ancestries. The results support more precise, population-aware models of early immune maturation that could inform timing and interpretation of pediatric immunologic biomarkers and interventions.
Dhillon BK, Blimkie TM, Idoko OT et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
Necroptosis triggers inflammatory interferon signatures in patient-derived metastatic breast cancer organoids.
This work used 3D patient-derived metastatic human mammary organoids to model apoptosis resistance and necroptosis, assessing inflammatory interferon signatures triggered by necroptosis. It found that inducing necroptosis in these organoids activates interferon-associated inflammatory programs consistent with DAMP-driven immunogenic cell death. The findings support necroptosis as a translational strategy to overcome apoptosis resistance in metastatic breast cancer and to identify interferon signatures as potential biomarkers of response.
Wächtershäuser KN, Schneider JV, Gessner A et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗
Insights into the therapeutic strategies for aging and aging-associated diseases.
This article reviewed therapeutic strategies aimed at modulating biological hallmarks of aging, including cellular senescence, metabolic dysfunction, epigenetic alterations, and mitochondrial impairment. It highlights three intervention classes—senolytics (e.g., dasatinib plus quercetin), senomorphics (e.g., rapamycin), and senescence-targeting approaches—proposed to delay aging and reduce risk of age-associated diseases. The synthesis provides a framework for selecting and combining aging-modifying therapies for neurodegeneration, metabolic disorders, and cardiovascular disease.
Dong R, Wu Q, Kan J et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗
Regulatory T cells in cancer and inflammation.
This review summarized the roles of regulatory T cells (Tregs) across cancer and inflammatory diseases, emphasizing how Treg function differs by context. It reports that in cancer Tregs suppress antitumor immunity and promote immune evasion, whereas in inflammatory diseases they limit excessive immune activation and support tissue repair, with dysfunctional Tregs contributing to chronic inflammation. The article frames Treg targeting as a therapeutic strategy for both oncology and inflammatory disorders, while underscoring the need for context-specific modulation.
Yang H, Zhang H, Xia N et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗
Multi-ancestry, trans-generational GWAS meta-analysis of gestational diabetes and glycaemic traits during pregnancy reveals limited evidence of pregnancy-specific genetic effects.
This multi-ancestry, trans-generational GWAS meta-analysis from the GenDiP Consortium evaluated gestational diabetes mellitus (GDM) and pregnancy glycemic traits using up to 38,305 GDM cases and 776,145 controls. It identified 37 GDM-associated loci (including 7 novel) and five novel loci for pregnancy glycemic traits, with evidence that effects act through the maternal genome and show pregnancy-dependent effect modification and diagnostic heterogeneity. These results refine the genetic architecture of GDM and clarify which variants may be pregnancy-specific, informing risk prediction and mechanistic studies for maternal metabolic disease.
Brito Nunes C, Rukins V, Cisse AH et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
Shared genetic architecture and pathways linking major depressive disorder and autoimmune thyroid disease: insights from common and rare variants.
This study used a population-matched UK Biobank cohort to investigate shared genetic architecture between major depressive disorder (MDD) and autoimmune thyroid disease (AITD) using GWAS summary statistics and polygenic risk score validation. It assessed genetic correlation, causal relationships, and pleiotropic loci/genes from common variants and complemented these with exome-wide association analysis from UK Biobank whole-exome sequencing data. The findings aim to explain the genetic basis of MDD–AITD comorbidity and prioritize candidate genes/pathways for mechanistic follow-up.
Liu S, Zeng Y, Xiao L et al. · Translational psychiatry · (2026) · View on PubMed ↗ · Free PDF ↗
Cryo-EM reveals multiple mechanisms of ribosome inhibition by doxycycline.
This cryo-electron microscopy study determined how doxycycline inhibits bacterial ribosomes by directly visualizing doxycycline binding sites in Coxiella burnetii and Escherichia coli. It found that doxycycline binds at the exit tunnel of the large subunit, with three stacked doxycycline molecules in C. burnetii, revealing multiple mechanisms beyond the canonical A-site tRNA-binding blockade. These structural insights can guide the design of next-generation tetracycline-like antibiotics to overcome resistance and exploit C. burnetii’s vulnerability.
Stuart WS, Isupov MN, McLaren M et al. · Nature communications · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗
Multi-omics analyses identify EZH2 as a central driver in rhabdomyosarcoma radioresistance and highlight Tazemetostat as an effective radiosensitizer in vitro and in vivo.
This multi-omics study in rhabdomyosarcoma (RMS) investigated mechanisms of intrinsic radiotherapy resistance and identified EZH2 as a central driver, using phosphoproteomics and transcriptomics in radioresistant RMS cell models. It reported that EZH2/PRC2-mediated gene silencing via H3K27me3 contributes to radioresistance and that the EZH2 inhibitor tazemetostat acts as an effective radiosensitizer in vitro and in vivo. Clinically, this supports EZH2 inhibition as a rational therapeutic strategy to improve radiotherapy outcomes in high-risk RMS.
Cassandri M, Porrazzo A, Camero S et al. · Cell death & disease · (2026) · View on PubMed ↗ · Free PDF ↗
Dual epitope anti-LILRB4 synthetic T-cell receptor and antigen receptor (STAR)-T-cell therapy for relapsed/refractory acute myeloid leukemia.
This preclinical study developed dual epitope anti-LILRB4 STAR-T cell therapy for relapsed/refractory acute myeloid leukemia (AML) by engineering nanobody-based synthetic T-cell receptor and antigen receptor constructs. It identified two high-affinity LILRB4 nanobodies via phage display and showed that dual epitope anti-LILRB4 STAR-T cells more potently inhibited AML in vitro and in vivo than comparator constructs. The approach targets the immunosuppressive receptor LILRB4 on monocytic AML blasts while sparing hematopoietic stem cells, supporting a potentially safer CAR-like strategy for AML.
Lv M, Zheng H, Pei X et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗
Digital Self-Management of Symptoms and Quality of Life for Patients With Advanced Cancer: A Randomized Clinical Trial.
This multicenter randomized clinical trial studied an app-facilitated palliative care intervention with digital symptom monitoring and nurse-led clinical follow-up in community-dwelling patients with advanced cancer receiving care at 6 palliative care clinics in Hong Kong. The intervention improved patient outcomes by better managing symptom burden and health-related quality of life compared with usual care (details truncated in the abstract). If confirmed in full results, this approach could reduce emergency department use and hospitalizations while scaling palliative support through digital monitoring plus clinician follow-up.
Chan WL, Soong IS, Lim MY et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗
Structural biology & molecular recognition
De Novo Design of Near-Infrared Fluorescence-Activating Proteins.
This chemical biology study aimed to de novo design near-infrared (NIR) fluorescence-activating proteins by integrating computational protein design with organic synthesis to create protein probes that work in long-wavelength optical windows. The key finding was the successful generation of proteins that specifically bind synthetic merocyanine dyes and form a Schiff base cofactor, enabling fluorescence activation in the targeted NIR/SWIR ranges. This is significant because it expands the toolkit of genetically encodable imaging proteins for deep-tissue biological fluorescence applications.
Liu Y, Arús BA, Mishra K et al. · Journal of the American Chemical Society · (2026) · View on PubMed ↗
High-resolution nuclear cell biology by cryo-electron tomography.
This review discussed how cryo-electron tomography (cryo-ET) enables high-resolution, in situ nuclear cell biology by visualizing nuclear architecture at sub-nanometer resolution. It summarizes how cryo-ET has advanced understanding of the 3D organization and dynamics of nuclear macromolecular assemblies involved in processes such as transcription, replication, and nucleocytoplasmic transport. The significance is methodological: cryo-ET is positioned as a key tool for mapping nuclear structure-function relationships in native cellular states.
Kechagia Z, Medalia O · Nucleus (Austin, Tex.) · (2026) · View on PubMed ↗ · Free PDF ↗
The auxin co-receptor TMK1-mediated phosphorylation and destabilization of DA1 connects auxin signaling with seed size control in Arabidopsis.
This study examined how auxin signaling controls seed size in Arabidopsis by identifying the auxin co-receptor TMK1 and its regulation of the seed-size inhibitor DA1. The authors found that TMK1 maternally regulates seed size by interacting with and phosphorylating DA1, destabilizing DA1 in an auxin-stimulated manner and thereby promoting auxin-promoted seed growth. The significance is mechanistic linkage of auxin perception (TMK1) to seed size control through post-translational regulation of DA1.
Wang A, Zheng L, Zhang X et al. · Molecular plant · (2026) · View on PubMed ↗
Structure of the E3 ligase CRL2ZYG11B with substrates reveals the molecular basis for N-degron recognition and ubiquitination.
This structural biology study determined cryo-electron microscopy structures of the cullin-2-RING ubiquitin ligase complex CRL2ZYG11B alone and bound to an NLRP1 Gly/N-degron peptide to define how ZYG11B recognizes substrates and couples them to ubiquitination. The structures show how ZYG11B’s leucine-rich repeat and armadillo repeat domains assemble with CRL2 and specifically engage the NLRP1 N-degron to enable ubiquitin transfer. These findings provide a molecular basis for N-degron recognition by CRL2ZYG11B and can inform strategies to modulate NLRP1 inflammasome regulation.
Liu X, Li Y, Castro LK et al. · Cell reports · (2026) · View on PubMed ↗
Environmental carcinogens & mutational signatures
Mutational signatures of environmental carcinogens in human tissue organoids revealed by duplex sequencing.
This study used human tissue-derived organoids exposed to a panel of environmental carcinogens and applied high-fidelity duplex sequencing (NanoSeq) to map mutational signatures without relying on clonal expansion. It generated a catalog of carcinogen-specific mutational signatures (including benzo[a]pyrene, aflatoxin B1, aristolochic acid I, and alkylating agents) that were consistent across multiple organ types including colon, stomach, liver, kidney, and pancreas. The work provides a direct, tissue-relevant way to quantify environmental carcinogen “molecular imprints,” improving attribution of mutational processes in human cancer.
Kucab JE, Nandi SP, Al-Serori H et al. · Cell reports · (2026) · View on PubMed ↗ · Free PDF ↗
Real-world drug safety & pharmacovigilance
Impact of appropriate antimicrobial therapy on patient outcomes and antimicrobial use: a sub analysis of the DIANA Study Dataset.
This predefined sub-analysis of the DIANA ICU dataset studied adult critically ill patients receiving empiric antimicrobials for suspected or confirmed bacterial infection, evaluating how “appropriate” empiric therapy affects outcomes and antimicrobial exposure. The key finding was that appropriate empiric antimicrobial therapy was associated with better patient outcomes and altered antimicrobial exposure compared with inappropriate therapy (restricted to patients with microbiologically confirmed infections). This supports antimicrobial stewardship by quantifying the clinical benefit of getting empiric therapy right in large international ICU cohorts.
Cidade JP, Póvoa P, Depuydt P et al. · Intensive care medicine · (2026) · View on PubMed ↗
Hypertension in autoimmune rheumatic diseases - a position paper from the ESH working group on small arteries.
This position paper from the ESH working group on small arteries reviewed hypertension management considerations in autoimmune rheumatic diseases (ARDs). It emphasizes that antirheumatic drugs can have variable effects on blood pressure and that standard diagnostic thresholds and therapeutic targets may not fully account for the markedly adverse cardiovascular risk profile in ARDs. The significance is a guideline-oriented synthesis to improve hypertension diagnosis and treatment decisions in ARD patients, accounting for both medication effects and elevated cardiovascular risk.
Gkaliagkousi E, Doumas M, Lazaridis A et al. · Journal of hypertension · (2026) · View on PubMed ↗
Prenatal exposure to asthma medications and risk of neurodevelopmental disorders and educational difficulties: A systematic review and meta-analysis.
This systematic review and meta-analysis evaluated whether prenatal exposure to asthma medications is associated with neurodevelopmental disorders and educational difficulties in offspring. Across included studies, the authors synthesized evidence using PRISMA/PECO methods to quantify associations between prenatal asthma drug exposure and later developmental outcomes. The findings inform risk-benefit considerations for continuing asthma therapy during pregnancy and guide future pharmacoepidemiologic research.
Shakhshir LA, Karain A, Pell JP et al. · PLoS medicine · (2026) · View on PubMed ↗ · Free PDF ↗
Comparative study of adverse drug reactions associated with anifrolumab and belimumab for the treatment of systemic lupus erythematosus.
This retrospective pharmacovigilance study compared adverse drug reactions associated with anifrolumab versus belimumab in patients with moderate-to-severe systemic lupus erythematosus using FDA Adverse Event Monitoring System (AEMS) Individual Case Safety Reports from 2011 to 2026. It extracted and coded ADRs for each biologic using anifrolumab/anifrolumab-Fnia and belimumab search terms to characterize and contrast real-world safety signals. The results are clinically significant for informing risk-benefit decisions between these two SLE biologics outside randomized trials.
Castellana E, Chiappetta MR · Lupus · (2026) · View on PubMed ↗
Cancer cell-cycle & differentiation mechanisms
Stage-Specific Degradation of Cyclin D3 Orchestrates Myelopoiesis and Restrains Myeloproliferative Neoplasms Development.
This mechanistic cancer biology study investigated how stage-specific degradation of cyclin D3 regulates myelopoiesis and constrains myeloproliferative neoplasm development, using a knock-in mouse expressing a degradation-resistant cyclin D3 variant (D3T283A). It found that preventing cyclin D3 degradation sustains cyclin D3 protein levels, promoting granulocyte-monocyte differentiation and altering normal myeloid control programs. These results highlight cyclin D3 turnover as a key regulatory checkpoint and suggest that disrupting cyclin D3 degradation can drive or modulate myeloid malignancy risk.
Mucha B, Tarallo V, Abbas A et al. · Cancer research · (2026) · View on PubMed ↗
Neurodegeneration & neuroinflammation (ALS/AD/PSP/brain biomarkers)
Global Consensus on Keratoconus and Ectatic Diseases-Edition 2.
This study updated a global consensus on keratoconus and ectatic corneal diseases by surveying 128 ophthalmologists from 12 international societies across 6 continents using a Delphi process plus a face-to-face meeting. The key outcome was an expert-agreed framework for defining, diagnosing, staging, and managing keratoconus/ectatic diseases, including surgical treatment recommendations, incorporating advances in newer technologies. This consensus standardizes clinical decision-making and improves comparability of research and care worldwide for patients with keratoconus and related ectatic corneal disorders.
Gomes JAP, Hafezi F, Ambrósio R et al. · Cornea · (2026) · View on PubMed ↗
Planimetric and Linear MRI Markers for Progressive Supranuclear Palsy Classification: A Large Multicohort International Study.
This large multicohort international study used planimetric and linear MRI measurements to classify progressive supranuclear palsy (PSP) and distinguish it from Parkinson disease and other parkinsonisms. The key finding was that specific planimetric/linear markers—derived from established midbrain line/area and ratios—performed differently for PSP versus non-PSP groups, enabling identification of an optimized linear MRI marker for classification. Scientifically and clinically, improved MRI-based discrimination can support earlier and more accurate PSP diagnosis and better stratification in research and trials.
Quattrone A, Bianco MG, Vescio B et al. · Radiology · (2026) · View on PubMed ↗ · Free PDF ↗
Regulatory factor X 7 limits Myc activity during B cell activation and suppresses Myc-dependent lymphomagenesis.
The study examined how Regulatory factor X 7 (RFX7) regulates Myc activity during B cell activation and whether RFX7 loss drives Myc-dependent lymphomagenesis in humans and mouse models. Rfx7 deletion in B cells increased Myc activity and enhanced germinal center B cell and plasmablast responses, accelerating diffuse large B cell lymphoma–like pathogenesis in Bcl6- and p53-loss models, and these effects were partially reversed by Myc haploinsufficiency. These findings identify RFX7 as a brake on Myc in B cells and suggest that Myc dosage may modulate prognosis and therapeutic vulnerability in RFX7-mutant diffuse large B cell lymphoma.
Fischer BA, Khameneh HJ, Guerra J et al. · Nature immunology · (2026) · View on PubMed ↗
Microtubule binding protein Togaram1 is required for proper development of mammalian forebrain and neural primary cilia.
This study investigated the role of the microtubule binding protein Togaram1 in mammalian forebrain development and neural primary cilia, focusing on how Togaram1 contributes to Joubert syndrome–associated phenotypes. Togaram1 was required for proper development of the mammalian forebrain and for correct formation/function of neural primary cilia. These findings are clinically significant because they strengthen the mechanistic link between TOGARAM1 dysfunction and neurodevelopmental disorders involving ciliopathy and microcephaly.
Nassar CQ, Shetty SJ, Dwyer ND · Developmental biology · (2026) · View on PubMed ↗
Predicting risk of mental health deterioration using multimodal data from the UK biobank.
This study used multimodal UK Biobank data to predict future mental health deterioration by integrating genetically informed and non-genetic features across 157,733 participants, including 2,911 plasma proteins, 2,126 brain imaging-derived phenotypes (IDPs), 77 lifestyle factors, and 103 mental health/cognitive questionnaire measures. The key finding was the development of predictive models that leverage polygenic risk score–based phenome-wide association signals and multimodal biomarkers to forecast symptom worsening. This is scientifically and clinically important because it supports earlier identification of individuals at risk for depression, anxiety, and cognitive decline for targeted intervention.
Yang S, Lv X, Huang B et al. · Journal of advanced research · (2026) · View on PubMed ↗ · Free PDF ↗
Longitudinal Change in Blood-Based Biomarkers and the Association With MRI-Measured Neurodegeneration in Cognitively Unimpaired Individuals.
This prospective observational study assessed longitudinal changes in blood-based Alzheimer disease biomarkers and their relationship to MRI-measured neurodegeneration in cognitively unimpaired individuals from the Amsterdam Subjective Cognitive Impairment Cohort. It found that temporal associations between biomarker trajectories and brain atrophy can be characterized longitudinally over ~5 years of follow-up. Scientifically, this supports using serial blood biomarkers to infer or anticipate neurodegenerative progression before cognitive impairment.
Trieu C, Dicks E, de Leeuw D et al. · Neurology · (2026) · View on PubMed ↗ · Free PDF ↗
miR-146a is a pleiotropic regulator of motor neuron degeneration.
This study profiled microRNAs in motor neurons during degeneration in vivo to define the role of miR-146a in amyotrophic lateral sclerosis (ALS), using SOD1G93A mice and comparing diseased motor neurons versus bulk tissue. Genetic deletion of miR-146a significantly extended survival in SOD1G93A mice, with the largest benefit in heterozygotes, and reduced spinal cord gliosis without preventing motor neuron loss. These findings suggest miR-146a is a pleiotropic regulator of ALS neurodegeneration and a potential therapeutic target, with some miR-146a knockout animals developing spontaneous paralysis.
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 ↗
Prescribing of anti-dementia medications in primary care: A retrospective cohort study in 1489 English General Practices.
This retrospective cohort study used English general practice data (1489 practices) to examine how patient-level characteristics and time trends influence prescribing of anti-dementia medications, focusing on acetyl cholinesterase inhibitors (AChEIs) and memantine. The key finding was that prescribing patterns varied with patient characteristics and over time, including rates of co-prescribing that were not fully captured by prior studies focused on all-cause dementia. These results highlight inequities and implementation gaps in guideline-recommended anti-dementia pharmacotherapy in primary care.
Morris C, Mok PLH, Robinson DL et al. · PloS one · (2026) · View on PubMed ↗ · Free PDF ↗
Neurovascular & brain small-vessel disease
Engineered Pericyte-Targeted Extracellular Vesicles Protect Against Hypoperfusion-Induced Cognitive Impairment and Vascular Demyelination.
This study developed pericyte-targeted extracellular vesicles (EVs) engineered with cyclic NGR (cNGR) peptides to treat vascular cognitive impairment (VCI) in a mouse model of chronic cerebral hypoperfusion. The cNGR-EVs selectively targeted CD13-expressing brain pericytes and preserved pericyte contractility, reduced blood–brain barrier leakage, attenuated demyelination, and improved cognitive performance in the BCAS model. Scientifically and therapeutically, it provides a targeted EV platform for protecting neurovascular unit function by restoring pericyte health under hypoperfusion.
Shen W, Liu W, Guo M et al. · Journal of extracellular vesicles · (2026) · View on PubMed ↗ · Free PDF ↗
A novel mouse model of cerebral microbleeds by targeted Col4a1 editing in adult brain microvessels.
This study developed a mouse model of cerebral microbleeds by targeted Col4a1 editing in adult brain microvessels, using Cas9 transgenic mice and brain endothelium-specific AAV-BR1 delivery of CRISPR/Cas9 components. Targeted deletion of Col4a1 in adult microvessels produced cerebral microbleed phenotypes, establishing a mechanistic in vivo system for cerebral small vessel disease. The model is scientifically significant because it enables causal testing of Col4a1-driven microvascular pathology and downstream pathways relevant to stroke and cognitive decline.
Kim H, Seo Y, Kho H et al. · Brain : a journal of neurology · (2026) · View on PubMed ↗
Metabolism, lipid handling & metabolic biomarkers
15-PGDH inhibition promotes muscle repair and strength recovery during GLP-1 receptor agonist-induced weight loss.
This study tested whether inhibiting the prostaglandin-degrading enzyme 15-PGDH (15-hydroxyprostaglandin dehydrogenase) can protect skeletal muscle during GLP-1 receptor agonist–induced weight loss, using a high-fat diet mouse obesity model treated with semaglutide. The key finding was that semaglutide caused significant muscle mass loss, but 15-PGDH inhibition promoted muscle repair and strength recovery while preserving contractile function in the setting of semaglutide. Clinically, it suggests a combinatorial approach to reduce the muscle side effects of GLP-1 receptor agonists such as long-acting semaglutide.
Nalbandian M, Lone J, Le Moal E et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗
Lifestyle-Induced Visceral Fat Loss as a Key Target for Durable Cardiometabolic Health: MRI-Assessed 5- and 10-Year Follow-Up After 2 Clinical Trials.
This study evaluated long-term (5- and 10-year) cardiometabolic outcomes after lifestyle interventions in participants from the CENTRAL and DIRECT-PLUS randomized clinical trials, using MRI-assessed visceral fat changes. It found that lifestyle-induced visceral fat loss was associated with more durable improvements in cardiometabolic health over extended follow-up. The clinical significance is that visceral fat reduction—quantified by MRI—may be a key target for long-term prevention of cardiometabolic deterioration after diet and exercise interventions.
Klein H, Alufer L, Goldberg Toren DT et al. · Circulation · (2026) · View on PubMed ↗ · Free PDF ↗
Estimated glucose disposal rate outperforms thirteen other insulin resistance indices in predicting new-onset cardiometabolic multimorbidity: a longitudinal study from the china health and retirement longitudinal study (CHARLS) and cross-sectional replication from the national health and nutrition examination survey (NHANES).
This longitudinal study assessed 14 surrogate insulin resistance (IR) indices for predicting new-onset cardiometabolic multimorbidity (CMM) in 8,522 CMM-free participants from the China Health and Retirement Longitudinal Study (CHARLS), with external replication in the U.S. NHANES. The estimated glucose disposal rate (eGDR) outperformed 13 other IR indices in predicting incident CMM. These findings support using eGDR as a more informative clinical surrogate of insulin resistance for risk stratification of cardiometabolic multimorbidity across populations.
Zhao E, Xie H, Wang R et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗
Unraveling ‘F’ factor: towards a genetic-clinical framework for the musculoskeletal-heart crosstalk in metabolic aging.
This study used the prospective CHARLS cohort to develop and validate a genetic-clinical framework centered on a frailty-linked “F factor” to explain musculoskeletal–heart crosstalk in metabolic aging and cardiometabolic multimorbidity (CMM). Using machine learning models, the authors created Frailty-Integrated Indices that improved prediction of CMM risk and captured systemic vulnerability linking cardiometabolic and musculoskeletal aging. The work is significant because it provides a testable, frailty-based integrative construct that could guide earlier identification and targeted interventions for multimorbidity in aging populations.
Zhou Y, Huang J, Chen X et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗
Oral Semaglutide 25 mg Versus Orforglipron 36 mg in Obesity: A Population-Adjusted Indirect Treatment Comparison.
This study indirectly compared oral semaglutide 25 mg versus orforglipron 36 mg for weight loss and cardiometabolic effects in adults with overweight or obesity without diabetes, using individual patient data from OASIS 4 and anchored indirect treatment comparisons with aggregate data from ATTAIN-1, with population-adjustment for baseline sex, body weight, and normoglycaemic status. The key finding was the relative efficacy and tolerability of semaglutide versus orforglipron in this adjusted cross-trial framework (with outcomes reported as percentage body-weight change and other biomarkers in ct. the abstract). These results are clinically relevant for selecting oral anti-obesity therapies by providing comparative effectiveness estimates when head-to-head trials are not available.
Michalak W, Bøg M, Bendixen T et al. · Diabetes, obesity & metabolism · (2026) · View on PubMed ↗
Muscle-derived ANXA2 promotes hepatic steatosis by activating SREBP1c-mediated de novo lipogenesis.
This study examined muscle–liver crosstalk in hepatic steatosis by testing whether muscle-derived annexin A2 (ANXA2) promotes liver fat accumulation through SREBP1c-mediated de novo lipogenesis, using mouse models of muscular dystrophy, FAP-specific ANXA2 knockout mice, and human muscle biopsy/serum data. The key finding was that ANXA2 signaling from muscle increases hepatic steatosis by activating SREBP1c-dependent lipogenic programs. This is clinically significant because it identifies ANXA2 as a potential therapeutic target to treat fatty liver disease associated with muscular dystrophy.
Wu P, Kiram A, Zhu Y et al. · Metabolism: clinical and experimental · (2026) · View on PubMed ↗
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 population in Taiwan using the Taiwan Precision Medicine Initiative database. It found novel genetic risk variants associated with early-onset ischemic stroke and used fine-mapping and linkage disequilibrium analyses to explore functional relevance (abstract truncated). These results improve understanding of stroke genetics in younger patients and can guide future functional studies and risk prediction in East Asian populations.
Wang YC, Liu KM, Gan YL et al. · Neurology · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗
GPIHBP1 on oligodendrocytes binds lipoprotein lipase within the human brain.
This study investigated how lipoprotein lipase (LPL) is captured in the human brain by testing whether GPIHBP1, a glycosylphosphatidylinositol-anchored protein, binds LPL on oligodendrocytes. Using single-nucleus RNA-seq resources and mechanistic experiments, the authors identified that GPIHBP1 on oligodendrocytes can bind LPL within the human brain. The work clarifies a CNS-specific pathway for LPL handling that may influence lipid availability for myelination and brain metabolism.
Liu M, Hung M, Kozlov E et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗
Polyunsaturated fatty acid-derived lipid mediator patterns determine viral pneumonia severity and risk for critical COVID-19.
This study analyzed white blood cell transcriptomes, targeted lipidomics, cytokine measurements, and immune cell profiling in relation to polyunsaturated fatty acid (ω6/ω3)-derived lipid mediator (LM) patterns around hospital admission in COVID-19 patients. The authors found that LM patterns were profoundly altered in COVID-19, correlated with inflammatory responses, and could stratify viral pneumonia severity and risk for critical disease. These results support lipid mediator profiling as a potential biomarker approach to predict COVID-19 severity and critical progression.
Papadaki M, Pavlos E, Dubourdeau M et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗
Immune modulation & tumor microenvironment (Tregs/immune evasion)
Myeloid Piezo1 Drives Cardiac Repair Through Orai1-Rac1-Dependent Efferocytosis.
This study investigated the myeloid-specific role of the mechanosensitive channel Piezo1 in post–myocardial infarction cardiac repair, using Piezo1ΔLysM knockout mice and left anterior descending coronary artery ligation. Myeloid Piezo1 promoted Orai1–Rac1-dependent efferocytosis, improving myocardial remodeling and cardiac function after infarction. Clinically, the findings identify a myeloid Piezo1–Orai1–Rac1 axis as a potential target to enhance macrophage clearance of apoptotic cells and improve outcomes after myocardial infarction.
Liu S, Xu H, Deng B et al. · Circulation research · (2026) · View on PubMed ↗
Unraveling the immune microenvironment in primary CNS lymphoma.
This review synthesized evidence on how the immune microenvironment—particularly tumor-infiltrating lymphocytes, tumor-associated macrophages, and dendritic cells—shapes primary CNS lymphoma (PCNSL) biology. It highlights that PCNSL is strongly influenced by immune-privileged-site interactions and that an immunosuppressive tumor microenvironment contributes to disease progression and treatment response. Understanding these immune microenvironment drivers is clinically significant for improving biomarker development and designing more effective immunomodulatory therapies in PCNSL.
Lorenzen S, Zeremski V, Berisha M et al. · Biomarker research · (2026) · View on PubMed ↗ · Free PDF ↗
CAR T cells for systemic autoimmune diseases.
This article reviewed the use of chimeric antigen receptor (CAR) T cells in systemic autoimmune diseases, emphasizing mechanistic principles and clinical experience including anti-CD19 CAR T cells. The key finding is that CAR T therapy can achieve meaningful clinical responses in severe refractory autoimmune conditions, with efficacy linked to CAR-mediated targeting and immune modulation. The review is significant for guiding future trial design and improving understanding of how CAR T cells can be safely and effectively repurposed beyond B-cell malignancies.
Rosetti F, Madera-Salcedo IK, Cenobio LA et al. · Autoimmunity reviews · (2026) · View on PubMed ↗
Autophagy Inhibition Reprograms the Tumor Microenvironment of Pancreatic Cancer to Promote Macrophage Phagocytosis of Tumor Cells.
This cancer research study investigated how autophagy inhibition in pancreatic ductal adenocarcinoma (PDAC) reprograms the tumor microenvironment to promote macrophage phagocytosis of tumor cells. It found that autophagy inhibition recruits macrophages via the CXCL1/2–CXCR2 axis and decreases the “don’t eat me” ligand CD47 on tumor cells, increasing susceptibility to macrophage phagocytosis. The findings suggest a mechanistic rationale for combining autophagy-targeting strategies with immunotherapies to enhance antitumor clearance in PDAC.
Lin EY, Mukhopadhyay S, Corcoran D et al. · Cancer research · (2026) · View on PubMed ↗
HLA micropolymorphisms confine neoantigen conformational adaptability and guide T cell receptor selectivity.
This PNAS study examined how micropolymorphisms within the HLA-A3 superfamily affect neoantigen conformational adaptability and T cell receptor (TCR) selectivity. It found that micropolymorphisms in two closely related HLA-A3 members (HLA-A03:01 vs HLA-A03:02) govern whether a public neoantigen–specific TCR can recognize the same epitope, despite similar peptide-binding expectations. Immunologically, the work clarifies how subtle HLA variation can reshape TCR repertoires and neoantigen recognition, with implications for personalized cancer vaccine design.
Ma J, Ayres CM, Brambley CA et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗
Adjuvant Nivolumab vs Observation in Resected Non-Small Cell Lung Cancer: A Randomized Clinical Trial.
This randomized phase 3 open-label clinical trial compared adjuvant nivolumab versus observation in patients with resected non-small cell lung cancer (NSCLC) after upfront surgery, stratified across any tumor PD-L1 expression and a subgroup with at least 50% PD-L1. The study evaluated whether adjuvant nivolumab improves disease-free survival and overall survival relative to observation, with long follow-up reported at the December 2025 data cutoff. If effective, adjuvant nivolumab could extend perioperative immunotherapy benefit to post-surgical management of resected NSCLC.
Chaft JE, Sun Z, Rudin CM et al. · JAMA · (2026) · View on PubMed ↗
Standardized End Point Definitions for Clinical Trials in Thoracic Aortic Repair: A Consensus Report From the ARCH-Academic Research Consortium.
This consensus report from the ARCH-Academic Research Consortium (ARCH-ARC) developed standardized endpoint definitions for clinical trials in thoracic aortic repair, covering ascending aorta and arch pathology treated with catheter-based and hybrid procedures. The key contribution was harmonizing consistent clinical trial endpoints and definitions across specialties and stakeholders to enable safe and comparable evaluation of new technologies. Standardized endpoints can reduce heterogeneity across studies and improve evidence quality for thoracic aortic interventions.
Beck AW, Desai ND, Abel D et al. · Circulation · (2026) · View on PubMed ↗
Immunotherapy clinical trials & rechallenge strategies
Antibody-drug conjugates in gynecologic cancers.
This narrative review evaluated the therapeutic strategy and clinical development of antibody-drug conjugates (ADCs) in gynecologic cancers, focusing on antigen-targeted monoclonal antibodies delivering cytotoxic payloads. It reports encouraging clinical activity across ovarian, cervical, and endometrial cancers using targets such as folate receptor alpha, HER2, and tissue factor. The review is significant for clinicians and researchers because it consolidates current ADC targets and trial directions to inform selection of patients and future combination strategies.
Barquin A, Kasherman L, Lheureux S et al. · Cancer · (2026) · View on PubMed ↗
Emerging Role of Radiopharmaceutical Therapy in Oncology: Advances, Challenges, and Future Directions.
This review summarized advances and challenges in radiopharmaceutical therapy (RPT) and the radiotheranostic paradigm, emphasizing molecularly targeted delivery of ionizing radiation with patient-specific imaging, dosimetry, and monitoring. It highlights that improved radioligand chemistry and pharmacokinetics have led to FDA approvals including [177Lu]Lu-PSMA-617 (Pluvicto®) for metastatic castration-resistant prostate cancer. The article is clinically significant because it frames how RPT can complement external beam radiotherapy and expand precision oncology through target discovery and optimized delivery.
Ordas L, Foster S, Pham P et al. · JNCI cancer spectrum · (2026) · View on PubMed ↗ · Free PDF ↗
Mapping the antibody-drug-conjugates landscape in non-small cell lung cancer: Where are we and where are we going?
This review mapped the current and future ADC landscape in non-small cell lung cancer (NSCLC), focusing on where agents are in clinical development and which biomarkers define responsive subsets. It emphasizes late-phase ADCs including trastuzumab deruxtecan (HER2), datopotamab deruxtecan and sacituzumab govitecan (TROP2), and patritumab deruxtecan (targeted by HER3). The synthesis is significant because it helps clinicians anticipate evolving ADC indications and informs trial design around target expression and resistance mechanisms.
Parisi C, Barlesi F, Planchard D · Cancer · (2026) · View on PubMed ↗
Chemotherapy for patients with circulating tumour DNA positive, stage II colon cancer (CIRCULATE) - an AIO / ABCSG trial.
This AIO/ABCSG CIRCULATE phase trial studied whether adjuvant chemotherapy improves disease-free survival in UICC stage II, pMMR/MSS colon cancer patients stratified by postoperative circulating tumor DNA (ctDNA) positivity using an academic tumor-informed NGS-based assay. In ctDNA-positive patients, participants were randomized 2:1 to capecitabine ± oxaliplatin (CHEMO) versus observation, while ctDNA-negative patients were randomized to observation versus an off-study approach, with the primary endpoint being DFS in ctDNA-positive patients. The trial is significant because it tests ctDNA as a biomarker to identify stage II patients most likely to benefit from adjuvant chemotherapy.
Folprecht G, Stasik S, Reinacher-Schick A et al. · Annals of oncology : official journal of the European Society for Medical Oncology · (2026) · View on PubMed ↗ · Free PDF ↗
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 phase 3 ASTRUM-006 trial studied perioperative serplulimab (anti–PD-1) combined with S-1 plus oxaliplatin (SOX) versus perioperative chemotherapy alone in PD-L1–positive, locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma, enrolling patients with PD-L1 CPS ≥5. The key finding was the comparative efficacy and safety of adding perioperative serplulimab to neoadjuvant and adjuvant SOX-based treatment in this randomized, double-blind, multicentre setting. The results are clinically important because they evaluate whether chemo-immunotherapy improves outcomes over standard perioperative chemotherapy in a biomarker-selected population.
Shen L, Zhang X, Ji K et al. · Lancet (London, England) · (2026) · View on PubMed ↗
[177Lu]Lu-dota-tate versus sunitinib in patients with metastatic progressive neuroendocrine tumours of the pancreas (OCLURANDOM): a randomised, controlled, phase 2 trial.
This phase 2 OCLURANDOM trial compared [177Lu]Lu-dota-tate versus sunitinib in adults with pretreated, progressive, somatostatin receptor–positive metastatic pancreatic neuroendocrine tumors. The key finding was the antitumor activity and safety profile of peptide receptor radionuclide therapy ([177Lu]Lu-dota-tate) relative to the tyrosine kinase inhibitor sunitinib in this randomized setting. This is significant because it informs optimal systemic therapy sequencing for metastatic pancreatic neuroendocrine tumors with somatostatin receptor expression.
Baudin E, Durand A, Beron A et al. · The Lancet. Oncology · (2026) · 1 citations · View on PubMed ↗
Aglatimagene besadenovec (CAN-2409) with radiotherapy for patients with localised prostate cancer: a phase 3, multicentre, randomised, double-blind, placebo-controlled trial.
This phase 3 randomized, double-blind, placebo-controlled trial evaluated whether adding aglatimagene besadenovec (CAN-2409; aglatimagene) plus valacyclovir to standard-of-care external beam radiotherapy improves disease-free survival in men with localized prostate cancer. The key finding was the effect of the gene therapy–radiotherapy combination on disease-free survival compared with radiotherapy plus placebo. This is clinically significant because it tests a strategy to enhance radiation efficacy and immune-mediated tumor control in curatively treated localized prostate cancer.
DeWeese TL, Manzanera A, Sylvester J et al. · The Lancet. Oncology · (2026) · View on PubMed ↗ · Free PDF ↗
PD-(L)1 containing rechallenge strategies in patients with advanced NSCLC previously treated with immunotherapy: A systematic review and meta-analysis across resistance phenotypes.
This systematic review and meta-analysis studied PD-(L)1 inhibitor rechallenge strategies in patients with advanced non-small-cell lung cancer (NSCLC) who previously received PD-(L)1–based immunotherapy, stratifying by resistance phenotypes. It concluded that clinical benefit from PD-(L)1 rechallenge remains uncertain based on the included trials across resistance categories. Clinically, the findings help define where PD-(L)1 rechallenge may or may not be justified and highlight the need for better biomarkers and trial designs.
Marinelli D, Citarella F, Torchia A et al. · Cancer treatment reviews · (2026) · View on PubMed ↗ · Free PDF ↗
Targeted cancer therapy & resistance modeling
Daraxonrasib Doubles OS for PDAC in Phase III Trial.
This report summarized results from a phase III trial testing daraxonrasib, a pan-RAS inhibitor, in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) as second-line therapy. Daraxonrasib doubled overall survival compared with chemotherapy, establishing it as a new standard-of-care for second-line metastatic disease. The significance is that RAS-targeted therapy with daraxonrasib can substantially improve survival in PDAC, motivating further RAS-targeted combination trials.
Cancer discovery · (2026) · View on PubMed ↗
Fovinaciclib for First-Line Therapy of Advanced Breast Cancer: A Randomized Clinical Trial.
This randomized clinical trial evaluated fovinaciclib (a CDK inhibitor) plus an aromatase inhibitor as first-line therapy in adult women with hormone receptor–positive, ERBB2-negative advanced breast cancer in China. The key finding was the trial’s efficacy and safety results for the combination regimen versus the control arm (details truncated in the abstract). If the benefits outweigh risks, this could expand first-line targeted options for HR+/ERBB2− advanced breast cancer.
Yuan P, Liu Y, Li W et al. · JAMA oncology · (2026) · View on PubMed ↗
A targeted combination therapy achieves effective pancreatic cancer regression and prevents tumor resistance.
This PNAS study tested a targeted combination therapy for pancreatic ductal adenocarcinoma (PDAC) using both genetic ablation and pharmacologic inhibition of KRAS pathway nodes. It found that genetic ablation of three downstream/upstream/orthogonal KRAS signaling nodes (RAF1, EGFR, and STAT3) produced complete and permanent regression of orthotopic Kras/Tp53 mutant PDAC, and that combining selective inhibitors (RMC-6236/daraxonrasib for KRAS, afatinib for EGFR family, and SD36 for STAT3) achieved complete regression and prevented tumor resistance (abstract truncated). The results support a multi-node blockade strategy to overcome rapid resistance 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) · 3 citations · View on PubMed ↗ · Free PDF ↗
Which evolutionary game-theoretic model best captures NSCLC dynamics?
This study compared which evolutionary game-theoretic mathematical model best captures non-small cell lung cancer (NSCLC) dynamics by fitting two-population models to in-vitro data tracking drug-sensitive and drug-resistant cells. Using conditions with and without the drug alectinib and cancer-associated fibroblasts (CAFs), the authors tested combinations of growth functions (logistic, Gompertz, von Bertalanffy) and drug efficacy terms (Norton–Simon, linear, ratio-dependent) to identify the best-fitting model. The modeling framework can improve prediction of treatment response and resistance mechanisms in NSCLC under microenvironmental influences.
Garjani H, Dubbeldam J, Staňková K et al. · PloS one · (2026) · 3 citations · View on PubMed ↗ · Free PDF ↗
Hematologic malignancies (AML/lymphoma/myelofibrosis) therapeutics & mechanisms
Ziftomenib with venetoclax and azacitidine in relapsed/refractory NPM1-mutated acute myeloid leukemia.
This report analyzed adults with relapsed/refractory NPM1-mutated acute myeloid leukemia (NPM1-m AML) treated in the KOMET-007 phase 1 trial with the menin inhibitor ziftomenib combined with venetoclax and azacitidine. The key finding was the observed clinical activity and tolerability of ziftomenib plus venetoclax/azacitidine across dose levels in this R/R NPM1-m AML population, with 600 mg selected for expansion. This is clinically significant because it tests a targeted menin inhibition strategy to improve outcomes in a genetically defined AML subgroup.
Wang ES, Erba HP, Zeidan AM et al. · Blood · (2026) · View on PubMed ↗
Selinexor Plus Ruxolitinib in JAK Inhibitor-Naïve Myelofibrosis: Phase 3 SENTRY Trial.
The SENTRY phase 3 trial studied JAK inhibitor–naïve myelofibrosis patients randomized to selinexor plus ruxolitinib versus placebo plus ruxolitinib, with co-primary endpoints of spleen volume reduction (SVR35) and change in total symptom score (AbsTSS excluding fatigue) at Week 24. The key finding was that adding selinexor to ruxolitinib improved the co-primary efficacy measures compared with ruxolitinib alone (as reported for the randomized 353-patient cohort). Clinically, this supports a potential combination regimen to enhance both spleen response and symptom control in treatment-naïve myelofibrosis.
Bose P, Ali H, Al-Ali HK et al. · Journal of clinical oncology : official journal of the American Society of Clinical Oncology · (2026) · View on PubMed ↗ · Free PDF ↗
Dynamic genetic and nongenetic RAS pathway activation drives resistance to FLT3 and BCL2 inhibitor therapy.
This study used multiomic single-cell DNA/protein and RNA/protein profiling to characterize dynamic genetic and nongenetic RAS pathway activation driving resistance in acute myeloid leukemia (AML) patients treated with venetoclax plus gilteritinib (Ven/Gilt). In a clinical trial cohort, the authors showed that resistance involved evolving transcriptional and immunophenotypic states alongside clonal genetic changes, with RAS pathway activation emerging as a key driver under therapy. These findings provide mechanistic targets for overcoming resistance to FLT3 and BCL2 inhibitor combinations in AML.
Kennedy VE, Peretz CAC, Walia A et al. · Blood · (2026) · View on PubMed ↗
DNA repair, chromatin & epigenetic regulation
ACMG/AMP variant classification specifications from the ClinGen Epilepsy Sodium Channel Variant Curation Expert Panel.
This work created ACMG/AMP variant classification specifications for epilepsy sodium channel genes (SCN1A, SCN2A, SCN3A, SCN8A, and SCN1B) through the ClinGen Epilepsy Sodium Channel Variant Curation Expert Panel. The key finding was that the panel adapted ACMG/AMP criteria using clinical, bioinformatic, and functional evidence and piloted modified rules on 37 variants spanning pathogenic, benign, and VUS categories. Scientifically and clinically, it standardizes how variants in these major epilepsy genes are classified, improving diagnostic consistency for patients with sodium channel–related epilepsies.
Smith L, Bonkowski E, Prentice A et al. · Genetics in medicine : official journal of the American College of Medical Genetics · (2026) · View on PubMed ↗
Therapeutic targeting of DNA repair pathway dysregulation in aging, cancer, and neurodegeneration.
This review analyzed how dysregulation of DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination, and end-joining variants) changes across aging, cancer, and neurodegeneration. It highlights that stresses such as oxidative damage, replication stress, telomere dysfunction, mitochondrial injury, and persistent DNA damage response signaling remodel these pathways and drive senescence and inflammation, creating context-specific vulnerabilities for therapy. The scientific significance is a framework for selecting DNA repair-targeted interventions tailored to disease mechanism and patient context across multiple conditions.
Kumar V, Kashif M, Singh V et al. · Expert opinion on therapeutic targets · (2026) · View on PubMed ↗
Deacetylated PCBP1 licenses PARP1 activity for DNA damage repair.
This study examined how the RNA-binding protein PCBP1 regulates PARP1-mediated DNA damage repair in physiological conditions, focusing on SIRT7-dependent post-translational control. It found that SIRT7 deacetylates PCBP1 at K314 and K351, weakening PCBP1’s inhibition of PARP1 and thereby licensing PARP1 activity during the early DNA damage response. These mechanistic insights identify a SIRT7–PCBP1 switch that could be exploited to modulate PARP1 function and improve genome-stability–based therapeutic strategies.
Shu Y, Zhang J, Zhou L et al. · Molecular cell · (2026) · View on PubMed ↗ · Free PDF ↗
NuRD-enabled CTCF-TET crosstalk orchestrates epigenome reprogramming and genome architecture.
This study investigated how DNA methylation and CTCF binding are coordinated to establish an ordered nucleosome and hypomethylated landscape, using a GpC methylation-assisted tracing (G-MAT) approach. It found that CTCF–chromatin interactions frequently coincide with methylated DNA and that the NuRD (nucleosome remodeling and deacetylase) complex is indispensable for CTCF chromatin binding. The work links NuRD-dependent chromatin remodeling to base-pair–level epigenome reprogramming, informing how 3D genome architecture is established.
Sun W, Wu N, Xia M et al. · Molecular cell · (2026) · View on PubMed ↗
Control of lipid metabolism in chondrocytes is critical for skeletal growth.
This PNAS study investigated the role of lipid/metabolic control in chondrocytes during skeletal growth, focusing on the ER stress regulator PPP1R15B. It found that PPP1R15B represses eIF2α phosphorylation to modulate stress translation, and that deletion of Ppp1r15b in Prx1+ skeletal progenitors (Ppp1r15bPrx1) or inducible deletion in Col2+ chondrocyte-lineage cells impairs chondrogenesis and causes skeletal growth defects in mice. These findings link ER-stress–coupled translational control to cartilage development, identifying PPP1R15B as a potential target for chondrodysplasia-related disorders.
John AA, Yang YS, Xie J et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗
Cell death pathways & innate immune activation (ferroptosis/necrotosis/NETs/STING)
Nociceptive neurons inhibit neutrophil extracellular trap formation via MLKL-licensed histone release.
The authors investigated how nociceptive dorsal root ganglion (DRG) neurons regulate neutrophil extracellular trap (NET) formation in neuroinflammation, focusing on MLKL (a necroptosis effector) and histone H3 release. They found that MLKL is constitutively nuclear in nociceptive neurons and binds histone H3, while peripheral inflammation disrupts the MLKL/H3 interaction, causing MLKL cytoplasmic translocation and extracellular histone H3 that drives NETs and hyperalgesia (via P2X7 and TLR4), and that nociceptive-specific Mlkl depletion reduces these effects. Scientifically, this links necroptosis machinery to pain-associated NET formation and suggests MLKL-pathway targeting as a potential strategy to mitigate chronic pain driven by neuroimmune crosstalk.
Meng H, Hu W, Kang E et al. · Cell reports · (2026) · View on PubMed ↗
A cytosolic IF1 reporter enables real-time visualization of severe mitochondrial membrane damage.
The researchers developed and validated MAI-1, a genetically encoded cytosolic IF1 reporter, to visualize severe mitochondrial membrane damage in real time across biological injury paradigms. They found that MAI-1, a Caenorhabditis elegans IF1 homolog lacking mitochondrial targeting, rapidly and irreversibly translocates from the cytosol to severely damaged mitochondria within milliseconds, and that cytosolic IF1 variants from other species show conserved recruitment. This provides a new tool for studying catastrophic mitochondrial injury dynamics and for probing mechanisms of mitochondrial integrity failure.
Gao E, Guan L, Zhang K et al. · The Journal of cell biology · (2026) · View on PubMed ↗ · Free PDF ↗
Ferroptosis promotes aortic stenosis through 5-lipoxygenase.
This study tested whether ferroptosis contributes to aortic stenosis via 5-lipoxygenase (5-LOX) and assessed translational relevance in human valve tissue. Using bulk and single-cell transcriptomics, whole-mount histology, immunohistochemistry, and primary human valvular interstitial cell (VIC) models from 212 surgical aortic valves, the authors linked iron-overload–associated valvular ferroptosis to 5-LOX and validated mechanistic and in vivo relevance in a doxorubicin-induced ferroptosis mouse model. The significance is identification of 5-LOX–linked ferroptosis as a druggable pathway for calcific aortic valve disease and aortic stenosis.
Qin Z, Haftbaradaran Esfahani P, Pawelzik SC et al. · European heart journal · (2026) · View on PubMed ↗
Emerging roles of ferroptosis in modulating the immune landscape of glial tumours.
This review examined how ferroptosis, an iron-dependent lipid peroxidation cell-death program, shapes immune-cell composition and function in glial tumors, focusing on resident microglia and tumor-infiltrating T cells. It reports that ferroptosis can polarize microglia and modulate CD8+ T-cell cytotoxicity while also influencing regulatory T-cell immunosuppressive effects, thereby contributing to immune evasion mechanisms in glioma. These insights suggest ferroptosis pathways as potential targets to reprogram the glioma immune microenvironment and improve immunotherapy responsiveness.
Argenziano MG, Neelakantan TV, Sperring C et al. · Nature cell biology · (2026) · View on PubMed ↗
A designed peptide disrupting viral protease cleavage restores cGAS-DNA phase separation and type I interferon responses.
This study developed and used a dimerization-dependent red fluorescent protein (ddRFP) biosensor to screen peptides that inhibit the Seneca Valley Virus (SVV) 3C protease. The authors identified a substrate-competitive decapeptide (P5) that markedly suppresses 3C protease activity and restores cGAS–DNA phase separation and type I interferon responses. This provides a peptide-based antiviral strategy that targets viral immune evasion and reactivates innate sensing pathways.
Yin H, Zhao Z, Wang H et al. · PLoS pathogens · (2026) · View on PubMed ↗ · Free PDF ↗
Generated automatically on June 03, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.