PubMed Trending Research Digest — June 10, 2026
A curated digest of 93 trending PubMed articles, automatically categorised and summarised across 15 research areas.
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PubMed Trending Research Digest — June 10, 2026
Automated digest · 93 articles · 15 research areas · June 10, 2026
Overview
This week’s digest is dominated by mechanistic studies that connect cellular stress, metabolism, and immune signaling to disease progression and therapy response. In cancer, multiple papers highlight how tumors remodel their microenvironments to evade immunity or resist treatment—e.g., fatty-acid recycling and TREM2+ lipid-associated macrophages in immune-checkpoint blockade–resistant hepatocellular carcinoma, metabolic axes such as USP1-driven lipophagy–lipogenesis in cholangiocarcinoma, and stress-linked transcriptional programs (like CEBPD/CXCL2 after insufficient ablation) that promote recurrence. Across hematologic and solid-tumor settings, there is also a strong emphasis on precision stratification—using biomarkers, immunogenomic classifiers, and imaging/genomics models to predict who benefits from which therapy.
A second major theme is “systems biology” approaches to regulation: from transcription–chromatin mechanics in neurons (RNAPII, CTCF/cohesin, and supercoiling) to RNA-mediated control of protein function (3′ UTR “chaperone” effects and condensate miscibility rules). Neurodegeneration papers further reinforce the idea that organelle dynamics and innate immune pathways matter—linking cGAS–STING signaling to Huntington disease phenotypes, autophagosome–mitochondria contact dysregulation in tauopathy, and α-synuclein fibril effects on mitochondrial structure and mitochondrial-derived vesicle biogenesis.
Finally, several clinical and translational studies focus on improving outcomes through better targeting and earlier intervention: updated cardiovascular–kidney–metabolic guidance and risk-based prevention strategies, new trials of GLP-1–pathway drugs for obesity/diabetes (including oral agents and pregnancy safety signals), and randomized/consensus efforts to standardize care (e.g., stroke post-reperfusion management, invasive cutaneous squamous cell carcinoma, and axillary staging after neoadjuvant chemotherapy). Together, the set underscores a broader shift toward individualized risk prediction, mechanism-informed therapy selection, and multi-modal measurement (omics, imaging, and spatial transcriptomics) to guide next steps.
DNA replication stress & genome stability
In Vivo CAR T-Cell Therapy Spurs 100% ORR in Phase I.
This phase I study evaluated the in vivo CAR T-cell therapy KLN-1010 in patients with multiple myeloma in the inMMyCAR trial. All 18 treated patients responded (100% ORR), and none of the evaluable patients had minimal residual disease 1 month after treatment. These results indicate strong early clinical activity for an in vivo CAR T approach and justify further development and longer follow-up.
Cancer discovery · (2026) · View on PubMed ↗
Bi-allelic loss-of-function variants in TMEM63B cause syndromic surfactant dysfunction disorder.
This genetic study examined the clinical effects of bi-allelic predicted loss-of-function variants in TMEM63B in humans with childhood interstitial lung disease. Five individuals from four unrelated families had early-onset respiratory distress, chronic hypoxemia, and diffuse parenchymal lung abnormalities, linking TMEM63B—an alveolar type II mechanosensitive ion channel involved in stretch-induced surfactant secretion—to syndromic surfactant dysfunction disorder. Identifying TMEM63B bi-allelic LoF as a cause improves molecular diagnosis and clarifies disease biology for surfactant-related lung disorders.
Chan SH, Iness AN, Rosenfeld JA et al. · American journal of human genetics · (2026) · View on PubMed ↗
Designing complex organoids through developmental principles.
This article reviewed how developmental biology principles can be used to design next-generation organoids with increased cellular complexity. It focuses on technical and conceptual advances that better reproduce in vivo developmental processes to generate organoid models containing more of the cell types needed to study normal development and disease. Scientifically, this framework supports more physiologically faithful organoid systems for mechanistic studies and translational modeling.
Brassard JA, Wells JM · Cell stem cell · (2026) · View on PubMed ↗
Human REV1 interacts with DHX36 to promote replication and tolerance of G-quadruplex DNA.
This study examined how human REV1 coordinates replication of G-quadruplex (G4) DNA in cells, focusing on REV1 interaction with the helicase DHX36 and the effects of G4 stabilization by pyridostatin (PDS). REV1 loss shifted fork elongation toward a PrimPol-driven pathway, impaired suppression of ssDNA gaps, increased nuclear G4 accumulation with elevated ATM/ATR signaling, and sensitized cells to G4-stabilizing agents, with leading-strand mutagenesis more affected than lagging-strand bypass and PDS sensitivity restricted to lagging-strand mutagenesis. These findings define a REV1–DHX36 replisome coupling mechanism that promotes G4 resolution, replication fidelity, and fork tolerance—highlighting potential targets for protecting genome stability under G4-stressing conditions.
Ketkar A, Paxton BC, Zuniga OE et al. · Nucleic acids research · (2026) · View on PubMed ↗ · Free PDF ↗
Meiotic recombination & fertility genetics
XPF-like domain in human SHOC1 is required for crossover formation and protecting autosome from MSUC.
This study investigated the role of the XPF-like domain of human SHOC1 in meiotic recombination and crossover formation in the context of the SHOC1–SPO16–TEX11 ZMM complex, including the clinically associated missense variant p.Q590R. The p.Q590R XPF-like variant disrupted DNA double-strand break repair by impairing formation/function of the SHOC1 complex needed for crossover (CO) formation, leading to defective recombination outcomes and failure to protect autosomes from meiotic single-strand–associated damage (MSUC). The work links a specific SHOC1 domain mutation to a mechanistic defect in human gametogenesis-relevant recombination, providing a molecular explanation for male infertility associated with SHOC1 variants.
Zhang Y, Sun Q, Ji Z et al. · Nucleic acids research · (2026) · View on PubMed ↗ · Free PDF ↗
Transcription–chromatin mechanics & genome organization
The atlas of abdominal organ remodeling in hepatocellular carcinoma patients: An artificial intelligence-based multicenter imaging study.
This multicenter deep learning imaging study analyzed abdominal CT scans to characterize organ remodeling in hepatocellular carcinoma (HCC) patients and to assess associations with treatment outcomes and prognosis. Using a deep learning algorithm to automatically segment organs (including spleen, liver, kidneys, pancreas, and adrenal glands) across 2,747 HCC patients and 2,869 healthy controls from 15 cohorts, the study evaluated patients treated with immune checkpoint inhibitors (ICIs), transarterial chemoembolization (TACE), or surgical resection. The resulting “atlas” could support AI-driven prognostication and treatment stratification in HCC based on quantitative abdominal organ changes.
Guo Y, Fu X, Li T et al. · Med (New York, N.Y.) · (2026) · View on PubMed ↗
RNAPII and DNA supercoiling regulate cohesin engagement in neurons.
This study analyzed how RNA polymerase II (RNAPII) activity and DNA supercoiling regulate cohesin engagement in cultured mouse cortical neurons by measuring occupancy of CTCF and cohesin subunits SMC1 and RAD21 relative to transcriptionally engaged RNAPII under stimulus-dependent transcription. CTCF and cohesin were enriched at transcription start sites (TSS) and increased with the level of engaged RNAPII, indicating that RNAPII promotes CTCF/cohesin occupancy, while changes in DNA supercoiling further modulated cohesin engagement. These results clarify how transcription-coupled chromatin mechanics in neurons coordinate CTCF/cohesin loading, informing models of genome organization and gene regulation in the brain.
Crewe M, Delint-Ramirez I, Halawa O et al. · Nucleic acids research · (2026) · View on PubMed ↗ · Free PDF ↗
Cancer biomarkers & precision oncology (clinical/omics)
TFH phenotype and response to tucidinostat in relapsed/refractory PTCL: analysis of patients from a phase IIb trial.
This retrospective analysis examined whether the T follicular helper (TFH) phenotype predicts response to the histone deacetylase inhibitor tucidinostat in relapsed/refractory peripheral T-cell lymphoma (PTCL), using patients from a phase IIb trial. It analyzed TFH-derived PTCLs including angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (NOS) to assess the predictive value of TFH phenotype across the PTCL spectrum. The significance is identifying a biomarker-linked subgroup that may better benefit from tucidinostat, supporting more personalized epigenetic therapy in PTCL.
Izutsu K, Fujimoto A, Rai S et al. · International journal of hematology · (2026) · View on PubMed ↗
Single-cell analysis reveals an endothelial TP53-CXCL14 axis in breast cancer progression.
The study used public datasets (TCGA, GEO, cBioPortal) plus in vitro TP53 perturbation in HUVEC cells to define how a TP53–CXCL14 axis relates to breast cancer progression and the tumor immune microenvironment. It found that TP53 regulates CXCL14 transcription (supported by ChIP-qPCR and dual-luciferase reporter assays) and that CXCL14 expression associates with prognosis and immune microenvironment features in breast cancer. This mechanistic axis provides a candidate biomarker and potential immunomodulatory target in breast cancer progression.
Chen W, Liu X, Li S et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗
A disease-centric vision-language foundation model for precision oncology in kidney cancer.
This study developed RenalCLIP, a disease-centric vision-language foundation model for precision oncology in kidney cancer, trained on 27,866 computed tomography (CT) scans from 8,809 patients across multi-center cohorts. RenalCLIP used two-stage pre-training to align domain-specific visual and textual representations and achieved improved performance and generalizability across ten clinical tasks including anatomical assessment, diagnostic classification, and survival prediction. The approach may reduce diagnostic uncertainty and improve decision-making for renal mass evaluation and prognostication.
Tao Y, Zhao Z, Wang Z et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
Structure and engineering of the large serine recombinase Bxb1 for gene integration.
This study investigated the structure and engineering of the large serine recombinase Bxb1 to enable DNA integration between attP and attB sites for genome engineering and gene therapy. Using cryo-electron microscopy, the authors resolved Bxb1-attP-attB synaptic complex structures in four functional states, explaining assembly into a tetrameric complex and an ~180° rotation that drives strand exchange and religation. These mechanistic structural insights can guide rational engineering of Bxb1 for improved gene integration tools.
Soma T, Hiraizumi M, Fell CW et al. · Molecular cell · (2026) · View on PubMed ↗
Deep Learning Predicts Mutations and Outcomes in Gastrointestinal Stromal Tumors from Whole-Slide Images.
The study used deep learning on gastrointestinal stromal tumor (GIST) whole-slide images (WSIs) to predict mutations and clinical outcomes across a large multi-center cohort (8398 cases from 21 centers) with molecular labels for many cases. The model enabled molecular classification, including distinguishing prognostic/therapeutic mutation patterns such as KIT exon 11 deletions versus wild-type, and improved outcome prediction compared with traditional risk modeling limitations. This demonstrates a scalable pathology-to-genomics approach that could guide TKI-related decision-making and prognostication in GIST.
Bonetti A, Le VL, Carrero ZI et al. · Cancer research · (2026) · View on PubMed ↗ · Free PDF ↗
Genomic hallmarks of depot medroxyprogesterone acetate-associated meningiomas.
The study defined genomic hallmarks of depot medroxyprogesterone acetate (DMPA)-associated meningiomas by integrating clinicopathologic data with targeted sequencing and DNA methylation profiling from tumors of 10 women with long-term DMPA exposure. Using classifier assignment, consensus clustering, copy number analysis, and differential methylation testing against reference cohorts, the authors identified DMPA-associated molecular features that distinguish these tumors from other meningioma groups. This clarifies the molecular basis of progestin exposure–linked meningioma risk and supports more precise classification of DMPA-associated disease.
Huq S, Gatesman TA, Abou-Al-Shaar H et al. · Neuro-oncology · (2026) · View on PubMed ↗
Cancer immunotherapy & immune evasion
Synergistic senolytic-regenerative therapy significantly extends healthspan and lifespan.
This preclinical study evaluated a combined senolytic-regenerative regimen using SenoVax™ dendritic-cell–based senolytic immunotherapy plus syngeneic pluripotent stem cell–derived mesenchymal stem cells (pMSCs) in mouse models of accelerated aging induced by carbon tetrachloride (CCl4) liver injury and doxorubicin-induced systemic senescence. The combination significantly reduced senescent cell burden and extended healthspan and lifespan compared with controls or single-modality treatments. The results support a translational rationale for pairing senolytic immunotherapy with regenerative MSC replacement to counteract senescence-associated secretory phenotype (SASP)–mediated anti-regeneration.
Ichim TE, Markov N, Lopes G et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗
Immunotherapy in bladder cancer: a systematic review of clinical trials and therapeutic advances.
This systematic review synthesized phase 2 and 3 clinical trial evidence for immunotherapies in bladder cancer, focusing on checkpoint inhibitors (pembrolizumab, atezolizumab, durvalumab), intravesical gene therapies (nadofaragene firadenovec, cretostimogene grenadenorepvec), and cytokine-based approaches. The review highlights therapeutic advances and summarizes efficacy/safety outcomes, particularly addressing limitations of BCG in non–muscle-invasive disease and the emergence of alternative immunotherapeutic strategies. Clinically, it provides an evidence map to guide selection and sequencing of bladder cancer immunotherapies beyond BCG failure.
Alasker A, Alghafees M, Nammor T et al. · BMC urology · (2026) · View on PubMed ↗ · Free PDF ↗
Efficacy and safety of toripalimab in combination with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): a phase 1b/2 study.
This open-label, multicenter phase 1b/2 trial evaluated toripalimab (anti–PD-1) combined with cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), including a platinum-refractory cohort and a previously untreated PD-L1–positive cohort. The study reported safety and efficacy outcomes with objective response rate as a primary endpoint and progression-free survival as a secondary endpoint. If confirmed in larger studies, the toripalimab–cetuximab combination could expand treatment options for R/M HNSCC, particularly in PD-1–targeted regimens.
Guo Y, Li Z, Xue L et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗
Functional screening of TCR-like antibodies using STAR-T cell library for cancer immunotherapy.
This study developed a functional screening platform for TCR-like antibodies using STAR-T synthetic T-cell receptor and antigen receptor libraries to identify tumor antigen–specific antibodies, including those targeting HLA-presented neoantigens. The key finding was that antigen engagement triggers synchronous receptor endocytosis and T-cell activation, enabling an “Endocytosis–Activation (E-A)” functional readout for antibody selection. Scientifically, this provides a scalable, function-based approach to discover effective TCR-like antibodies for cancer immunotherapy beyond affinity-only screening.
Li Y, Huang D, Liu C et al. · EMBO molecular medicine · (2026) · View on PubMed ↗ · Free PDF ↗
GPR15-guided CD8+ T regulatory cells control intestinal inflammation.
This study investigated intestinal inflammation control by identifying GPR15 as a marker and homing receptor for a subset of intramucosal GPR15-guided regulatory CD8+ T cells (CD8+ TIGR) in the context of inflammatory bowel disease. It found that GPR15-guided CD8+ regulatory T cells control intestinal inflammation, and that deleterious GPR15 gene variants impair their homing and are associated with severe early-onset IBD. The clinical significance is that GPR15-dependent trafficking of regulatory CD8+ T cells may represent a mechanistic target for improving IBD therapies.
Cui J, Chen Z, Cheng YH et al. · Nature · (2026) · View on PubMed ↗
Targeting ATF4 overcomes dual resistance to chemo-immunotherapy in gastric cancer by disrupting the DNA damage response.
This study aimed to overcome dual resistance to chemo-immunotherapy in gastric cancer (GC) by targeting activating transcription factor 4 (ATF4) and disrupting the DNA damage response. Integrative analyses of single-cell RNA sequencing and bulk transcriptomic datasets identified ATF4 as a key regulator of chemo-immunotherapy resistance, and functional validation was performed in GC cell lines, patient-derived organoids (PDOs), and patient-derived xenograft (PDX) models. By implicating ATF4 in DNA damage response–linked resistance mechanisms, the findings suggest ATF4 as a candidate biomarker and therapeutic target for improving GC chemo-immunotherapy outcomes.
Ye H, Zhang W, Cao H et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗
Tumor cells metabolically resist immune-checkpoint therapy by macrophage efferocytosis-mediated fatty acid recycling.
This study examined how hepatocellular carcinoma (HCC) tumor cells adapt to immune-checkpoint blockade (ICB) resistance in patients, focusing on macrophage efferocytosis and fatty acid recycling. In ICB-resistant HCC, serial tumor biopsies showed increased tumor-cell fatty acid uptake and up-regulation of TREM2+ lipid-associated macrophages (LAMs), and myeloid-specific Trem2 deficiency or anti-TREM2 antibody disrupted fatty-acid-dependent energy production and resensitized resistant tumors. These findings identify a macrophage efferocytosis–TREM2–fatty acid recycling axis as a mechanistic vulnerability that could be therapeutically targeted to overcome ICB resistance in HCC.
Liang Z, Long X, Xiong Z et al. · Cancer cell · (2026) · View on PubMed ↗ · Free PDF ↗
An immunogenomic classification of solid tumours reveals subtype-specific therapeutic vulnerabilities for immunotherapy.
This study developed an immunogenomic classification to predict response to immune checkpoint blockade (ICB) and identify subtype-specific therapeutic vulnerabilities in solid tumors. Using RNA-seq across 13 public ICB cohorts plus an in-house cohort, the authors trained ImmPred, a seven-gene classifier aligned to IHC-defined immune phenotypes, and integrated it with tumor mutational burden (TMB) to define immunogenomic subtypes with distinct resistance mechanisms. The approach aims to improve patient stratification beyond immune-inflamed/excluded/desert categories and to guide combination therapies tailored to each immunogenomic subtype.
Zhao Y, Wang P, Han Z et al. · EBioMedicine · (2026) · View on PubMed ↗ · Free PDF ↗
Modeling immune responses to autologous and allogeneic human stem cell-derived islet grafts in vivo.
The study modeled immune responses to autologous versus allogeneic stem cell-derived islet (SC-islet) grafts in human immune system mice transplanted with SC-islets and analyzed them 14–18 weeks later using imaging mass cytometry. Allogeneic SC-islet grafts showed distinctive graft features (including a high fraction of glucagon+ cells and cysts with CD57+ enterochromaffin cells) and exhibited heavy immune infiltration consistent with graft rejection dynamics. These findings provide an in vivo humanized framework to dissect how immune cells infiltrate and reject SC-islet grafts, informing immunomodulatory strategies for type 1 diabetes cell therapy.
Bechi Genzano C, Zanetti G, Du Q et al. · JCI insight · (2026) · View on PubMed ↗ · Free PDF ↗
Cancer cell biology & tumor microenvironment remodeling
High resolution spatial transcriptomics identifies insufficient radiofrequency ablation induces hepatocellular carcinoma progression via CEBPD / CXCL2 axis.
This study used high-resolution spatial transcriptomics to analyze hepatocellular carcinoma (HCC) tissue after insufficient radiofrequency ablation (iRFA) and to define molecular pathways driving progression. It identified a CEBPD/CXCL2 axis as a key transcriptional mechanism linking sublethal heat stress to an immunosuppressive tumor microenvironment and recurrence. Scientifically, it provides a spatially resolved mechanism for iRFA failure and suggests potential targets (CEBPD/CXCL2) to prevent post-ablation HCC progression.
Lin K, Zhang N, Zhang Z et al. · Hepatology (Baltimore, Md.) · (2026) · View on PubMed ↗
KRT14 Drives Basal Muscle-Invasive Bladder Cancer Progression and Lung Metastasis by Directly Binding to and Stabilizing IGF2BP1.
The study investigated how KRT14 drives basal muscle-invasive bladder cancer (BMIBC) progression and lung metastasis, using integrative analyses of clinical cohorts and BBN-induced mouse models and mechanistic binding studies of KRT14 and IGF2BP1. KRT14 directly binds and stabilizes IGF2BP1 by interacting residues K294/E295 in IGF2BP1’s KH2 domain with conserved residues D226/E227 in KRT14’s nuclear export signal, promoting IGF2BP1 cytoplasmic trafficking and auto-stabilization of its own mRNA. This identifies the KRT14–IGF2BP1 axis as a mechanistic therapeutic target for aggressive BMIBC and metastasis.
Huang S, Zhou Z, Xie Q et al. · Advanced science (Weinheim, Baden-Wurttemberg, Germany) · (2026) · View on PubMed ↗ · Free PDF ↗
SIRT3 regulates mitochondrial metabolism through deacetylation of SLC25A6 to impact gastric cancer progression and drug resistance.
This study investigated how mitochondrial sirtuin-3 (SIRT3) regulates gastric cancer progression and cisplatin (DDP) resistance by deacetylating the mitochondrial carrier SLC25A6 in gastric cancer models. The authors found that SIRT3-mediated deacetylation of SLC25A6 drives mitochondrial metabolic changes that promote tumor progression and chemoresistance. These findings suggest targeting the SIRT3–SLC25A6 axis could be a mechanistic strategy to overcome DDP resistance in gastric cancer.
Meng W, Lang C, Gan J et al. · Journal of translational medicine · (2026) · View on PubMed ↗ · Free PDF ↗
USP1-mediated lipophagy-lipogenesis axis drives cholangiocarcinoma progression and immune evasion.
This study investigated cholangiocarcinoma (CCA) progression and immune evasion by defining a USP1-mediated lipophagy–lipogenesis metabolic axis. Using untargeted metabolomics to identify key metabolite classes and next-generation sequencing with database analysis to identify the relevant molecular drivers, the authors linked metabolic reprogramming to immune suppression in the CCA tumor microenvironment. The work supports USP1/lipid-metabolism targeting as a potential TME-directed therapeutic strategy to counter immune evasion.
Chen Y, Xu X, Shao S et al. · Journal for immunotherapy of cancer · (2026) · View on PubMed ↗ · Free PDF ↗
Cucurbitacin B targets PPAT to suppress de novo purine biosynthesis in esophageal squamous cell carcinoma.
This study investigated whether phosphoribosyl pyrophosphate amidotransferase (PPAT), the rate-limiting enzyme of de novo purine biosynthesis (DNPB), drives esophageal squamous cell carcinoma (ESCC) progression and therapy response, using single-cell RNA sequencing and untargeted metabolomics. Cucurbitacin B was reported to target PPAT and suppress DNPB, producing PPAT-associated metabolic changes that reduced ESCC growth and potentially improved radiosensitivity/therapeutic response. The work supports PPAT as a druggable metabolic node in ESCC and positions cucurbitacin B as a candidate for targeting DNPB to enhance treatment efficacy.
Jia H, Guo J, Luo H et al. · Phytomedicine : international journal of phytotherapy and phytopharmacology · (2026) · View on PubMed ↗
A pan-cancer single-cell analysis of intratumoral copy number diversity and evolution.
The study performed a pan-cancer single-cell analysis of intratumoral copy number alteration (CNA) diversity and evolutionary dynamics across 94 tumors (seven cancer types) using single-cell copy number profiling, bulk exome sequencing, and single-nucleus RNA-seq. Increased subclonal diversity was associated with higher CNA burden, whole-genome doubling, and TP53 mutations, indicating that genomic instability and specific driver alterations shape intratumoral evolution. These findings provide a single-cell resolution map of how aneuploidy evolves within tumors, informing models of progression and potential biomarkers of aggressive evolution.
Ye H, McDonald TO, Elghaish R et al. · Cancer discovery · (2026) · View on PubMed ↗
Cancer therapeutics & clinical trials (non-immunotherapy)
New perspectives on endocrine therapy suitability for hormone receptor-positive metastatic breast cancer in clinical practice.
This article reviews clinical characteristics and biomarkers (including ESR1 and PIK3CA mutations and endocrine receptor expression) that may determine suitability, response, and optimal sequencing of endocrine therapy (ET) plus cyclin-dependent kinase 4/6 inhibitors in patients with hormone receptor-positive/HER2-negative metastatic breast cancer. It highlights that evolving evidence supports more individualized prediction of ET benefit across lines of therapy using these biomarkers and emerging clinical factors. The clinical significance is improved treatment selection and sequencing to maximize benefit and avoid ineffective ET strategies in this heterogeneous metastatic population.
Rugo HS, Curigliano G, Cescon DW et al. · Breast (Edinburgh, Scotland) · (2026) · View on PubMed ↗
European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma: Part 2. Treatment - update 2026.
This European consensus guideline update evaluates evidence and expert recommendations for treating invasive cutaneous squamous cell carcinoma (CSCC) in immunocompetent and immunosuppressed patients. It updates first-line management for common primary CSCC (with emphasis on appropriate surgical and adjuvant approaches) and refines treatment recommendations across patient immune status. The significance is standardized, multidisciplinary care across Europe to improve outcomes and reduce variability in invasive CSCC treatment.
Stratigos AJ, Dessinioti C, Garbe C et al. · European journal of cancer (Oxford, England : 1990) · (2026) · View on PubMed ↗
Intra-Arterial Alteplase After Successful Endovascular Reperfusion in Acute Stroke: The PEARL Randomized Clinical Trial.
This randomized clinical trial studied whether intra-arterial alteplase given after successful endovascular reperfusion improves functional outcomes in patients with acute anterior-circulation large-vessel occlusion stroke. It tests the added value of intra-arterial thrombolysis after thrombectomy success compared with the control strategy in the same clinical window. The significance is clarifying an important post-reperfusion treatment question that could affect stroke care pathways and outcomes.
Yang X, He X, Xu Y et al. · JAMA · (2025) · 11 citations · View on PubMed ↗ · Free PDF ↗
Pharmacologic Therapies for Patent Ductus Arteriosus in Extremely Preterm Infants.
This comparative effectiveness study evaluated pharmacologic regimens for patent ductus arteriosus (PDA) in extremely preterm infants (<29 weeks’ gestation), comparing standard-dose and adjustable-dose ibuprofen, indomethacin, acetaminophen, and conservative management. It aims to determine relative effectiveness among drug strategies and to compare outcomes between pharmacotherapy-treated and conservatively managed infants. The clinical significance is informing evidence-based PDA medication choice and reducing practice variation in a high-risk neonatal population.
Mitra S, Jain A, Ting JY et al. · JAMA network open · (2026) · View on PubMed ↗ · Free PDF ↗
A modified Delphi consensus on tenosynovial giant cell tumour and giant cell tumour of bone : a report from the Birmingham Orthopaedic Oncology Meeting (BOOM).
This modified Delphi consensus study gathered international experts to define key clinical and research priorities for tenosynovial giant cell tumour (TGCT) and giant cell tumour of bone (GCTB). Using 21 consensus statements debated by 314 delegates from 59 countries, it reached unanimous and strong consensus on multiple topics and identified one area with only moderate consensus. The significance is harmonized guidance for clinicians and a clearer roadmap for future research in these rare bone and soft-tissue tumors.
Jeys LM, Botello E, Boyle R et al. · The bone & joint journal · (2026) · View on PubMed ↗
Comparative effectiveness and safety of sarilumab vs Janus kinase inhibitors in late- and younger-onset rheumatoid arthritis.
This multicentre real-world cohort study compared sarilumab versus Janus kinase inhibitors (JAKi) in adults with late-onset RA (LORA) and young-onset RA (YORA), assessing 12-month changes in methotrexate dose and glucocorticoid dose. The study found differential effectiveness and safety patterns between sarilumab and JAKi that varied by age at onset, informing age-stratified treatment selection. Clinically, it supports tailoring GC/MTX-sparing biologic or targeted therapy choices based on whether RA begins in youth or later life.
Nozaki Y, Kishimoto K, Itami T et al. · Rheumatology (Oxford, England) · (2026) · View on PubMed ↗
BRAF-altered glioma in adults and children: A Society for Neuro-Oncology (SNO) and European Society for Neuro-Oncology (EANO) consensus review on clinical management and future directions.
This SNO–EANO consensus review synthesized evidence for clinical management of BRAF-altered glioma across WHO grades and treatment lines in both adults and children. It concludes that targeted BRAF-directed therapies are available and increasingly used, but the evidence quality varies across randomized trials, single-arm studies, and real-world data. The review provides an age- and grade-aware framework to guide diagnosis and treatment decisions for BRAF-altered diffuse gliomas.
Schreck KC, de la Fuente MI, Fat MJL et al. · Neuro-oncology · (2026) · View on PubMed ↗
Effect of subcutaneous foslevodopa/foscarbidopa therapy on non-motor symptoms in advanced PD patients.
This retrospective clinical study assessed whether subcutaneous foslevodopa/foscarbidopa (LDp/CDp) infusion improves non-motor symptoms (NMS) in 21 patients with advanced Parkinson’s disease over 3 weeks and again after 9 weeks. The key finding was that LDp/CDp therapy was associated with measurable improvements in NMS outcomes captured by MDS-UPDRS Part I and an NMS questionnaire. Clinically, it extends the evidence base for LDp/CDp beyond motor fluctuations and dyskinesias to include non-motor benefit in advanced PD.
Jander A, Bergner S, Schönwald B et al. · Journal of neurology · (2026) · View on PubMed ↗ · Free PDF ↗
Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial.
This randomized phase 3 trial (ALTAIR within CIRCULATE-Japan) studied whether initiating adjuvant therapy based on tumor-informed circulating tumor DNA (ctDNA) molecular recurrence improves outcomes in ctDNA-positive patients with resected colorectal cancer, assigning participants to trifluridine/tipiracil (FTD/TPI) versus placebo for 6 months. The key finding was the trial’s effect of ctDNA-triggered post-adjuvant FTD/TPI on the primary endpoint (molecular recurrence–guided strategy outcomes) compared with placebo. The significance is that it tests whether early, ctDNA-informed intervention can improve survival-related endpoints beyond standard surveillance after curative CRC resection.
Bando H, Watanabe J, Takahashi Y et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗
Targeting Cancer-Specific Mutations with RNA-Triggered Chromatin Shredding.
This study developed an RNA-triggered chromatin shredding strategy using CRISPR-Cas12a2, an RNA-guided nuclease with trans-nucleolytic cleavage, to selectively kill cancer cells by targeting cancer-specific transcripts. The key finding was that RNA-guided Cas12a2 trans shredding of chromatin induces DNA damage responses and cell death, enabling selective growth inhibition without requiring druggable protein pockets. The significance is a new therapeutic paradigm for targeting mutations indirectly at the RNA level to trigger lethal chromatin damage in cancer cells.
Zeng J, Cheng Z, Chen H et al. · Nature · (2026) · View on PubMed ↗
Engineering an AIEgen-based platform integrating CRISPR/Cas9 to remodel the tumor microenvironment and reinforce photo-immunotherapy against glioblastom.
This preclinical study engineered an aggregation-induced emission luminogen (AIEgen)-based platform integrating CRISPR/Cas9 to remodel the glioblastoma tumor microenvironment and enhance photo-immunotherapy. The authors designed a nanomedicine/gene-editing strategy intended to overcome blood–brain barrier (BBB) and tumor microenvironment barriers, using the AIEgen component (NDA-DP, as described) to support photo-activation alongside CRISPR/Cas9-mediated remodeling. If validated experimentally, this platform could improve the efficacy of photo-immunotherapy in glioblastoma by coupling gene editing with light-triggered immune reinforcement.
Luo G, Ma F, Yang Y et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗
International consensus on axillary staging after neoadjuvant chemotherapy in node-positive breast cancer.
This international consensus study addressed axillary staging after neoadjuvant chemotherapy (NAC) in node-positive breast cancer, focusing on minimally invasive techniques including targeted axillary dissection (TAD), marked lymph node biopsy (MLNB), and sentinel lymph node biopsy (SLNB). Through a Delphi-like process with consultant breast surgical oncologists from OECD countries and consensus defined by ≥70% agreement (with latent class analysis of surgeon characteristics), the paper aimed to standardize eligibility thresholds and technical standards for these approaches. Establishing consistent criteria could reduce variability in post-NAC axillary management and improve staging accuracy while minimizing overtreatment.
Lucocq J, Karakatsanis A, Kirwan C et al. · European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology · (2026) · View on PubMed ↗
12-month outcomes of photobiomodulation in dry age-related macular degeneration: a prospective multicentre randomised double-masked controlled clinical trial.
This multicentre, randomised, double-masked controlled trial studied 78 patients (138 eyes) with early or intermediate dry age-related macular degeneration (dAMD) receiving photobiomodulation (PBM) over 12 months, with mean drusen volume (MDV) as the primary outcome. PBM was assessed for its ability to change retinal anatomy and function by measuring MDV from baseline to 12 months and evaluating secondary functional endpoints (details truncated in the abstract). If PBM reduces drusen volume and preserves visual function, it would represent a non-invasive, disease-modifying strategy for early/intermediate dAMD where no approved progression-modifying therapy currently exists.
Iovino C, Borrelli E, Coco G et al. · The British journal of ophthalmology · (2026) · View on PubMed ↗
Comparative effectiveness and safety of pharmacological treatments for rapid tranquilisation in emergency settings: a systematic review and individual participant data network meta-analysis.
This systematic review with individual participant data network meta-analysis compared intramuscular and intravenous pharmacological options for rapid tranquilisation in patients with psychomotor agitation in emergency settings. The study synthesized randomized trial evidence using sedation within 15–30 minutes as the primary outcome to support evidence-based recommendations across treatment choices. Clinically, this approach aims to reduce variability in emergency sedation practices by identifying which drugs and routes most reliably achieve timely sedation and acceptable safety.
Siafis S, Philipona F, Nomura N et al. · The lancet. Psychiatry · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗
Scalp cooling outcomes in patients receiving trastuzumab deruxtecan for metastatic breast cancer.
This prospective phase II trial studied whether scalp cooling (SC) using the Paxman Scalp Cooling System prevents alopecia in patients with metastatic breast cancer receiving trastuzumab deruxtecan (T-DXd). Patients chose SC or no-SC arms, and the primary outcome was hair loss rate during T-DXd treatment. The trial addresses a clinically important toxicity-management question by testing an evidence-based intervention to reduce T-DXd–associated alopecia.
Salehi E, Chu X, Mayer EL et al. · ESMO open · (2026) · View on PubMed ↗ · Free PDF ↗
Hematologic malignancies & targeted cell therapies
Alternative Splicing of TPM1 Mediated by SRPK3 Drives Cardiac Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction.
The study examined whether TPM1 alternative splicing mediated by SRPK3 contributes to cardiac diastolic dysfunction in heart failure with preserved ejection fraction (HFpEF), using transmission electron microscopy, nanoindentation, genetically engineered AAV9 mouse models, and human pluripotent stem cell-derived cardiomyocytes. It found that SRPK3-driven TPM1 splicing alters cardiomyocyte mechanics associated with impaired diastolic function, linking specific splicing regulation to HFpEF pathology. This supports SRPK3–TPM1 splicing as a potential molecular lever for diagnosing or targeting diastolic dysfunction in HFpEF.
Chen Q, Wang X, Yin Z et al. · Circulation · (2026) · View on PubMed ↗
Therapeutic Outcomes in VEXAS Syndrome: A Multicenter Comparative Cohort of Allogeneic Hematopoietic Stem Cell Transplantation and Hypomethylating Agents.
This multicenter retrospective cohort compared outcomes of hypomethylating agents (HMA) versus allogeneic hematopoietic stem cell transplantation (alloHSCT) in 66 patients with VEXAS syndrome. Among evaluable alloHSCT recipients, all achieved molecular remission, and overall mortality was reported with deaths occurring in both groups (alloHSCT n=3; HMA n=11). The comparative data support alloHSCT as a potentially more effective disease-control option for selected VEXAS patients, while HMA remains an alternative for others.
Fathima S, Wong MM, Gonzalez-Lugo J et al. · American journal of hematology · (2026) · View on PubMed ↗
A novel CD7-directed antibody-drug conjugate targeting BCL-XL with potent anti-leukemic activity in T-cell acute lymphoblastic leukemia.
This preclinical study designed a CD7-directed antibody-drug conjugate (ADC-CD7-BCL-XLi) carrying a BCL-XL-selective inhibitor to treat T-cell acute lymphoblastic leukemia (T-ALL), addressing limitations of existing BCL-XL inhibitors caused by on-target thrombocytopenia. The ADC was engineered to target CD7+ T-ALL cells while selectively delivering BCL-XL inhibition, producing potent anti-leukemic activity in the reported models. The approach is clinically significant because it aims to preserve the efficacy of BCL-XL targeting while reducing the thrombocytopenia that has constrained prior BCL-XL inhibitor therapies.
Oliveira ML, Nuantang K, Huré G et al. · Leukemia · (2026) · View on PubMed ↗
Neurodegeneration & synuclein/tau/mitochondria/autophagy
Ultrastructural diversity and subcellular organization of nigral Lewy pathology in Parkinson’s disease.
This correlative light and electron microscopy study examined phosphorylated alpha-synuclein at serine 129 (αSynpS129) inclusions in the substantia nigra of end-stage postmortem brains from patients with Parkinson’s disease. Somatic αSynpS129 inclusions in nigral dopaminergic neurons were consistently fibrillar, while membranous-type inclusions were restricted to neuritic processes with ultrastructural heterogeneity ranging from predominantly membranous to mixed membranous-fibrillar forms. These findings refine the subcellular pathology map of Lewy pathology and may inform mechanistic models of alpha-synuclein aggregation and spread.
Lewis AJ, van den Heuvel L, Di Fabrizio M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
Multimodal biomarker characterization of amnestic objective subtle cognitive decline in aging and preclinical Alzheimer’s disease.
This study characterized amnestic objective subtle cognitive decline (obj-SCD) in aging and preclinical Alzheimer’s disease (AD) using multimodal biomarkers in the ALFAs+ prospective observational cohort. Across cognitively unimpaired individuals with baseline CSF biomarkers (normal vs AD continuum), longitudinal neuropsychological decline over 3 years was used to define obj-SCD, linking it to AD-relevant biomarker patterns. The results help refine early identification of individuals at risk for progression to preclinical AD and support multimodal biomarker strategies for detecting subtle cognitive change.
López-Martos D, Cacciaglia R, Suárez-Calvet M et al. · The journal of prevention of Alzheimer’s disease · (2026) · View on PubMed ↗ · Free PDF ↗
Alpha-synuclein fibrils induce budding of mitochondrial-derived vesicles.
The study investigated how α-synuclein fibrils affect mitochondrial structure and mitochondrial-derived vesicle (MDV) biogenesis in SH-SY5Y cells using high-resolution electron microscopy. Exposure to α-syn fibrils caused defects in mitochondrial cristae and increased budding of mitochondrial-derived vesicles compared with controls. This provides a mechanistic bridge between α-syn aggregation and mitochondrial dysfunction, highlighting MDV formation as part of synucleinopathy-related cellular toxicity.
Braun T, Reber V, Tiberi C et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗
Targeting the cGAS-STING pathway mitigates Huntington disease pathogenesis in a knock-in mouse model.
The study tested whether inhibiting the cGAS-STING innate immune DNA-sensing pathway mitigates Huntington disease (HD) pathogenesis by genetically ablating cGAS in Q175DN knock-in HD mice and performing longitudinal behavioral assessments from 2 to 14 months. cGAS deletion significantly improved HD motor deficits (rotarod and beam-walk) and mitigated progressive body-weight loss. These results establish cGAS as an in vivo contributor to HD phenotypes and support targeting cGAS-STING signaling as a potential therapeutic strategy.
Kesharwani A, Dagar S, Zuniga I et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗
Dysregulation of autophagosome-mitochondria contacts contributes to autophagy dysfunction and neurodegeneration in tauopathy.
The study characterized how autophagosome–mitochondria contacts contribute to autophagy dysfunction and neurodegeneration in tauopathy neurons, identifying the contact release factor TBC1D15 and upstream mitochondrial bioenergetic signaling. In tauopathy, autophagosome/autophagic vacuole–mitochondria contacts were hypertethered, which impaired AV retrograde transport, and this was attributed to accelerated TBC1D15 turnover driven by AMPK hyperactivity induced by mitochondrial bioenergetic deficits. This mechanistic model connects disrupted organelle contact dynamics to neurodegeneration and highlights AMPK–TBC1D15 regulation as a potential intervention point.
Jia N, Guan H, Zuo Y et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗
Neural circuits, sleep, and behavior
A cross-species atlas of the dorsal vagal complex reveals neural mediators of the effects of cagrilintide on energy balance.
The study generated a cross-species, spatially resolved transcriptomics atlas of the rat dorsal vagal complex (DVC) using single-cell transcriptomics across rat, mouse, and macaque to identify neural mediators of the amylin receptor agonist cagrilintide’s effects on energy balance, focusing on Calcr-expressing neuronal populations. Cagrilintide regulated two conserved Calcr-expressing DVC neuronal populations, with acute effects on gene expression in area postrema Calcr/Ramp3 neurons but no long-term food intake or body-weight change after chemogenetic activation in rats. These findings refine the neural circuitry downstream of cagrilintide and suggest that acute Calcr/Ramp3 transcriptional responses may not be sufficient to drive sustained therapeutic weight-loss effects.
Ludwig MQ, Coester B, Gordian D et al. · Nature metabolism · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗
First-line durvalumab in combination with trastuzumab deruxtecan in women with locally advanced unresectable or metastatic, hormone-receptor-negative, HER2-low breast cancer: multicenter, open-label, phase 1b/2 BEGONIA platform trial.
This study reconstructed a densely mapped adult Drosophila connectome uniting the brain and ventral nerve cord and used it to investigate distributed neural control circuits. It identified principles of control showing that effector neurons (including motor and endocrine effectors) are organized across brain-and-cord pathways rather than being confined to a single region. The scientific significance is that it provides a mechanistic framework for how distributed connectome architecture can implement flexible control in a vertebrate-like brain–spinal cord organization.
Schmid P, Im SA, Nowecki Z et al. · Nature cancer · (2026) · View on PubMed ↗ · Free PDF ↗
TMEM63B regulates nucleocytoplasmic transport and placental development.
This study identified TMEM63B, an osmo/mechano-sensitive ion channel, as a regulator of trophoblast cell cycle progression and placental development in models of placental biology. TMEM63B loss disrupted nucleocytoplasmic transport by destabilizing nuclear transport components, impairing Ran protein expression and the Ran-XPO1 complex and thereby blocking nuclear export of CDKN1A/p21, which led to defective trophoblast proliferation and placental dysfunction. The results suggest TMEM63B-mediated nucleocytoplasmic transport as a mechanistic lever for controlling trophoblast development.
Cai M, Lai R, Zheng W et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
Advances in the management of ADHD in children and adolescents.
This narrative review synthesized evidence (2019–2025) on diagnosing and managing attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, emphasizing a dimensional/pleiotropic model and comorbidity patterns. It reports that semi-structured interviews outperform rating scales for diagnosis, while neuroimaging and other biological tests have limited diagnostic utility and neuropsychological testing helps contextualize symptoms within cognitive developmental profiles. Clinically, the review supports more individualized, sustained care combining psychosocial interventions with improved diagnostic approaches for pediatric ADHD.
Robaey P, Rogers MA, Schachar RJ · BMJ (Clinical research ed.) · (2026) · 1 citations · View on PubMed ↗
Generation of human appetite-regulating neurons and tanycytes from pluripotent stem cells.
This study generated human appetite-regulating neurons and tanycytes from pluripotent stem cells by controlling BMP exposure timing and duration to produce VMH and arcuate nucleus (ARC) cell fates. The authors identified SHH-/NKX2.1+/FGF10+/RAX+/TBX3+ posterior tuberal progenitors as the source of ARC lineages, including AGRP-, PNOC-, GHRH-, and TRH-expressing neurons and β2-tanycytes, with differentiated ARC cultures showing transcriptomic similarity to human ARC. This provides a stem-cell-based platform to model human hypothalamic appetite circuits for studying energy-balance disorders and testing therapies.
Abay-Nørgaard Z, Mueller AK, Hänninen E et al. · Cell stem cell · (2026) · View on PubMed ↗ · Free PDF ↗
Developmental and age-related synapse elimination is mediated by glial Croquemort.
This study investigated how glial Croquemort (Crq) mediates developmental and age-related synapse elimination in Drosophila. Using a high-throughput ELISA-based in vivo screening assay, the authors identified Crq as an essential glial regulator of synapse elimination, where glial Crq loss caused excess CNS synapses and progressive seizure susceptibility in adults. The findings highlight a conserved glial mechanism for synapse pruning that may inform understanding of neurodevelopmental and neurodegenerative circuit dysfunction.
Jay TR, Kang Y, Ouellet-Massicotte V et al. · Neuron · (2026) · 1 citations · View on PubMed ↗ · Free PDF ↗
Prefrontal gamma oscillations engage dynamic cell-type-specific configurations to support flexible behavior.
This study examined how prefrontal gamma oscillations in mice support flexible behavior through dynamic, cell-type-specific neural configurations. Using dual-color voltage indicators and optogenetics, the authors showed that parvalbumin interneurons (PVIs) generate gamma-frequency activity that is recruited in a configuration-dependent manner to support prefrontal cortex–mediodorsal thalamus communication. Mechanistically, this links PVI-driven gamma dynamics to behavioral flexibility, informing potential circuit-targeted interventions for disorders such as schizophrenia.
Phensy AJ, Hagopian LL, Costello CM et al. · Neuron · (2026) · View on PubMed ↗ · Free PDF ↗
Active zone plasticity couples sleep need to presynaptic hypophosphorylation.
The study investigated how sleep need is coupled to presynaptic active zone plasticity in Drosophila by linking it to presynaptic hypophosphorylation, using synapse-enriched integrated-omics and prior brp gene copy number paradigms. Proteomic and bioinformatic analyses identified molecular changes consistent with active zone remodeling during sleep pressure, including alterations in pathways related to immune/stress responses (as reported in the abstract). This advances understanding of the synaptic molecular basis of sleep homeostasis by connecting sleep need to presynaptic active zone state changes.
Piao C, Dutkiewicz EP, Kollipara L et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗
RNA biology & gene regulation (including condensates)
Opposing roles of serine and charge in IDR condensate miscibility.
This biophysical study examined how amino-acid chemistry controls miscibility of intrinsically disordered region (IDR) condensates by analyzing 28 IDRs across 378 pairwise combinations. The authors found that serine and aromatic residues promote miscibility, whereas charged amino acids drive immiscibility, with mutagenesis confirming causality and simulations/network analyses explaining interaction preferences. These mechanistic rules provide a framework for predicting and engineering condensate behavior, including regulation by serine phosphorylation.
Pei G, Wang X, Quan X et al. · Nature chemical biology · (2026) · View on PubMed ↗
mRNA 3’ UTRs chaperone intrinsically disordered regions to control protein activity.
This study tested whether human mRNA 3’ UTRs can regulate protein activity by acting as “chaperones” for intrinsically disordered regions (IDRs). For MYC, UTX, and JMJD3, the authors found that their 3’ UTRs control protein activity, and for KDM6B they showed co-translational effects on JMJD3 folding—promoting IDR-IDR interactions and suppressing folding between structured domains. These results support a new RNA-based mechanism for controlling protein function beyond abundance or localization.
Luo Y, Zhong Y, Basu S et al. · Cell · (2026) · View on PubMed ↗
Protein homeostasis & proteostasis
Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.
This article is a mechanistic review on proteostasis that synthesizes how protein homeostasis networks—chaperones, ubiquitin–proteasome, autophagy–lysosomal pathways, and organelle-specific quality control—maintain cellular function and how their collapse drives disease. It highlights proteostasis disruption as a unifying pathological hallmark across neurodegenerative disorders, cancer, cardiovascular disease, and other human conditions. By bridging mechanisms and therapeutics, it frames actionable targets for interventions aimed at restoring or modulating proteostasis.
Borlepawar A, Neu M, Ma Z et al. · Signal transduction and targeted therapy · (2026) · View on PubMed ↗ · Free PDF ↗
Metabolism, inflammation & immune-metabolic axes
G-protein regulatory network governs receptor internalization dynamics.
This mechanistic study investigated how the G-protein regulatory network controls receptor internalization dynamics for G-protein-coupled receptors (GPCRs). It shows that regulation of the G-protein cycle shapes GPCR internalization behavior through defined principles and mechanisms. The scientific significance is improved understanding of how upstream GPCR signaling is tuned in space and time, informing models of GPCR signaling and trafficking.
Rowe JB, Pandey S, Mayer RA et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗
Integrative multi-omics analysis identifies endocrine-disrupting chemical-related molecular mechanisms in migraine.
This integrative multi-omics and causal inference study examined endocrine-disrupting chemical (EDC)–related molecular mechanisms contributing to migraine risk, using a curated set of 181 EDCs and 1,116 EDC-associated genes derived from chemical–gene interaction network analyses. The key finding was identification of EDC-linked genes and pathways that plausibly mediate migraine susceptibility, consistent with hormonal disruption as a mechanistic contributor to migraine. Scientifically, it provides candidate EDC–gene mechanisms that can be prioritized for functional validation and risk stratification in migraine research.
Ren Y, Xu Z, Xu Z et al. · The journal of headache and pain · (2026) · View on PubMed ↗ · Free PDF ↗
The embryonic origins of site-specific arthritis.
This study investigated why inflammatory arthritis is site-specific in humans by analyzing fetal finger joints, comparing proximal interphalangeal (PIP) joints (prone to inflammatory arthritis) with distal interphalangeal (DIP) joints (spared). Using single-cell RNA sequencing, imaging, and X-ray tomography, the authors found PIP joints had larger synovial volume and were enriched for PI16+ “universal” fibroblasts located in perivascular regions and at tendon–ligament interfaces. The work suggests developmental cellular programs help establish joint susceptibility, informing how site-specific inflammation may be predetermined.
Davidson S, Simone D, Jansen K et al. · Nature immunology · (2026) · View on PubMed ↗ · Free PDF ↗
Acacetin ameliorates MASLD by inhibiting the Notch1 pathway in hepatocytes and reprogramming macrophage polarization via Keap1-Nrf2-mediated restraint of ferroptosis.
This mechanistic preclinical study tested whether acacetin ameliorates metabolic dysfunction-associated steatotic liver disease (MASLD) by targeting the Notch1 pathway in hepatocytes and macrophage ferroptosis control, using male C57BL/6J mice fed a high-fat diet plus RAW264.7, BMDM, and AML12 cell models. Acacetin reduced hepatic lipid accumulation and necroptosis, suppressed Notch1 signaling in hepatocytes, and reprogrammed macrophages from an M1-like to an M2-like phenotype via Keap1–Nrf2-mediated restraint of ferroptosis (with additional details truncated). These findings suggest acacetin as a candidate multi-target therapy for MASLD that links hepatocyte signaling (Notch1) to immune polarization and ferroptosis regulation.
Xu J, Ying H, Wang Y et al. · Metabolism: clinical and experimental · (2026) · View on PubMed ↗
Biological and mechanistic pathways of cardiometabolic multiple long-term conditions.
This Lancet Series paper examined biological and mechanistic pathways underlying cardiometabolic MLTC, integrating evidence across the life course. It highlights shared mechanisms such as insulin resistance, adiposity, and chronic inflammation, and notes that long-term exposure to air pollutants (fine particulate matter, nitrogen dioxide) and early-life exposures (undernutrition/overnutrition, gut microbiome changes, endocrine-disrupting chemicals) can accelerate MLTC trajectories (details truncated). Mechanistic clarity is important for targeting prevention and treatment strategies that address common upstream drivers of multimorbidity.
Lim LL, Jenkins A, Prabhakaran D et al. · Lancet (London, England) · (2026) · 3 citations · View on PubMed ↗
PARK7-Mediated Delactylation of SF3B Reprograms RNA Splicing to Attenuate Fibrosis and Promote Antitumor Immunity.
This study investigated the role of PARK7 (DJ-1) in lactylation-dependent regulation of RNA splicing and its impact on fibrosis and antitumor immunity. Using lactylome analysis and immunoprecipitation–mass spectrometry, the authors identified PARK7 as a delactylase that delactylates SF3B2 at lysine 280 (K280), and RNA immunoprecipitation sequencing showed lactylation-driven abnormal splicing of serpin-family transcripts that promoted tumor growth. The findings link PARK7–SF3B2 delactylation to attenuation of fibrosis and enhanced immune-dependent antitumor responses, suggesting a potential therapeutic axis.
Sun L, Zhou Y, Zhao X et al. · Cancer research · (2026) · View on PubMed ↗
Lactate programs CRIP1 protein lactylation to drive synovial proliferation in rheumatoid arthritis.
The study examined lactate-driven protein lactylation in rheumatoid arthritis (RA) patients and tested how this modification promotes synovial hyperplasia, focusing on the lactylated protein CRIP1. RA synovium showed increased lactate production and increased protein lactylation that correlated with clinical disease activity, and CRIP1 lactylation was identified as a central driver of synovial proliferation. This links altered glycolysis/lactate metabolism to CRIP1 lactylation as a mechanistic pathway and potential therapeutic target in RA.
Ma M, Zhou Y, Li Q et al. · JCI insight · (2026) · View on PubMed ↗ · Free PDF ↗
Cardiovascular–kidney–metabolic risk & prevention
2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
This 2026 AHA/ACC/ADA/ASN guideline synthesizes evidence for prevention, detection, evaluation, and management of cardiovascular-kidney-metabolic syndrome across clinical care settings. It expands and replaces prior obesity-focused guidance by providing an integrated framework for clinicians managing interrelated obesity/type 2 diabetes, chronic kidney disease, and cardiovascular disease. The significance is a unified, guideline-based approach to risk stratification and coordinated management across these overlapping conditions.
Ndumele CE, Rodriguez F, Dixon DL et al. · Circulation · (2026) · View on PubMed ↗
Use of Predicted Risk and Expected Benefit to Guide Decision-Making in Cardiovascular-Kidney-Metabolic Syndrome for the Primary Prevention of Cardiovascular Disease: A Scientific Statement From the American Heart Association and American College of Cardiology.
This AHA/ACC scientific statement evaluates how predicted risk and expected benefit can guide primary prevention decisions for cardiovascular disease in patients with cardiovascular-kidney-metabolic risk. It emphasizes using quantitative risk assessment—specifically PREVENT (Predicting Risk of Cardiovascular Disease Events) equations—to align initiation and intensification of antihypertensive and lipid-lowering therapies with individual risk. The clinical significance is more precise, benefit-targeted preventive treatment selection rather than uniform guideline thresholds.
Khan SS, Bhave N, Blumenthal RS et al. · Circulation · (2026) · View on PubMed ↗
Semaglutide showed limited improvements in patients with Alzheimer’s disease: Revisiting the evoke and evoke + clinical trials.
This article revisited the phase 3 Evoke and Evoke+ Alzheimer’s disease trials of semaglutide, focusing on additional time points beyond the originally analyzed week-104 CDR-SB results. While the week-104 intermediate readout was negative and led to trial failure, later unreported/unanalyzed CDR-SB data at weeks 130 and 156 showed separation favoring semaglutide over placebo. The findings suggest semaglutide’s efficacy signal in Alzheimer’s disease may have been underestimated due to timing of statistical analyses.
Hölscher C · Journal of Alzheimer’s disease : JAD · (2026) · View on PubMed ↗
Differential associations between novel triglyceride-glucose-obesity indices and incident stroke in individuals with early-stage cardiovascular-kidney-metabolic syndrome: a longitudinal cohort study.
This longitudinal cohort study assessed whether six novel triglyceride–glucose–obesity indices (TyG-CVAI, TyG-BRI, TyG-CI, TyG-WWI, TyG-ABSI, TyG-RFM) predict incident stroke in individuals with early-stage cardiovascular–kidney–metabolic (CKM) syndrome stages 0–3. It compared the strength of associations across indices for stroke risk, aiming to identify which composite measure best stratifies future cerebrovascular events. The results could improve risk prediction and prevention strategies by selecting the most informative TyG–obesity metric for early CKM patients.
Fu ZQ, An L, Zhang W et al. · Cardiovascular diabetology · (2026) · View on PubMed ↗ · Free PDF ↗
Electronic cigarette use after smoking cessation and lung cancer risk.
This cohort study evaluated lung cancer risk after smoking cessation in 4,524,895 adults in the Korean National Health Screening Program, using baseline 2018 e-cigarette use to define post-cessation e-cigarette exposure and follow-up through December 2023. The key finding (as assessed in multivariable models) was the association between post-cessation daily e-cigarette use and subsequent lung cancer incidence and lung cancer-specific death. Scientifically, it clarifies whether e-cigarette use after quitting conventional cigarettes changes lung cancer risk, informing harm-reduction guidance for former smokers.
Kim YW, Park EJ, Kwak KI et al. · Nature medicine · (2026) · View on PubMed ↗
Effects of SGLT2 inhibition on incident heart failure in carriers of cardiomyopathy-associated genetic variants.
This analysis used whole-exome sequencing data from the randomized DECLARE–TIMI 58 trial to test whether SGLT2 inhibition with dapagliflozin versus placebo reduces incident heart failure hospitalization in carriers of pathogenic or likely pathogenic variants in cardiomyopathy-associated genes. The study compared treatment effects on hospitalization for heart failure between carriers and noncarriers of high-confidence cardiomyopathy gene variants. Clinically, it addresses whether SGLT2 inhibitors confer benefit across genetic cardiomyopathy risk strata, supporting or refining precision approaches to HF prevention in patients with type 2 diabetes.
Marston NA, Kany S, Melloni GEM et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗
Apitegromab for lean mass preservation during tirzepatide-induced weight loss: a randomized, double-blind, placebo-controlled phase 2 trial.
This randomized, double-blind, placebo-controlled phase 2 trial (EMBRAZE) studied whether apitegromab, a myostatin-activation inhibitor monoclonal antibody, preserves lean mass during tirzepatide-induced weight loss in adults with overweight or obesity (n=102). At week 24, apitegromab plus tirzepatide resulted in less lean mass loss than tirzepatide plus placebo (reported least-squares mean difference of 1.9 kg less lean mass loss). The clinical significance is that combining tirzepatide with myostatin inhibition may improve the body-composition profile of incretin-based obesity therapy by mitigating muscle loss.
Pratley RE, Denham DS, Trivedi R et al. · Nature medicine · (2026) · View on PubMed ↗ · Free PDF ↗
Development of risk assessment models for microvascular complications in type 2 diabetes mellitus patients: a cross-sectional study.
This cross-sectional retrospective study developed and validated nomogram risk estimation models for microvascular complications—diabetic retinopathy (DR) and diabetic kidney disease (DKD)—in 6,043 patients with type 2 diabetes mellitus (T2DM). Using LASSO regression to select predictors from 38 clinical/laboratory variables followed by multivariate logistic regression, the authors built DR/DKD risk nomograms. These models could support individualized screening and risk stratification for DR and DKD in routine T2DM care.
Lin Y, Zhan Z, Zheng K et al. · Scientific reports · (2026) · View on PubMed ↗ · Free PDF ↗
Understanding sugar-sweetened beverage tax implementation globally: a 34-year, population-based observational study in 183 countries.
This 34-year, population-based observational analysis aggregated global datasets from 1990–2024 to characterize sugar-sweetened beverage (SSB) tax implementation across 183 countries and identify national predictors of policy adoption. It evaluated how tax characteristics relate to factors such as SSB intake, disease burden, and economic development (results truncated in the abstract). Understanding which contexts drive adoption can guide policymakers in designing and implementing SSB taxes to improve population cardiometabolic health.
Loaeza LM, Lara-Castor L, Sharib JR et al. · The Lancet. Global health · (2026) · View on PubMed ↗ · Free PDF ↗
A quarter-century of progress: innovations in lipid medicine that transformed cardiovascular prevention.
This TimeCapsule review summarized major innovations in lipid medicine over the past quarter-century that transformed cardiovascular prevention, focusing on how LDL-cholesterol lowering strategies evolved from statin-centric care to include non-statin agents and biological therapies. It emphasizes the clinical significance of lowering LDL earlier and sustaining reductions over time to achieve greater cardiovascular risk reduction, and highlights emerging RNA- and DNA-targeted approaches (details truncated). The review supports current prevention paradigms and frames future directions for precision lipid-lowering therapies.
Masana L, Ribalta J, Ibarretxe D · The lancet. Diabetes & endocrinology · (2026) · View on PubMed ↗
Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with type 2 diabetes (SOLSTICE): a multicentre, phase 2b, randomised, placebo-controlled trial.
The SOLSTICE phase 2b trial studied elecoglipron, an oral small-molecule GLP-1 receptor agonist, in adults with type 2 diabetes using a multicentre, randomised, double-blind, placebo-controlled design across nine countries. It compared elecoglipron versus placebo to evaluate efficacy, safety, and tolerability over the trial period (primary/secondary outcomes truncated in the abstract). If effective and well tolerated, elecoglipron could expand oral GLP-1–based options for type 2 diabetes management beyond injectable therapies.
Aroda VR, Davies MJ, Maaske J et al. · Lancet (London, England) · (2026) · View on PubMed ↗
Interventions for the prevention and management of cardiometabolic multiple long-term conditions.
This Lancet Series paper reviewed interventions to prevent and manage cardiometabolic multiple long-term conditions (MLTC), organizing evidence into population-level, individual-level, and system-level approaches. It argues that grouping cardiometabolic MLTC is justified because shared antecedents and risk factors enable overlapping therapeutic strategies that can improve prevention, treatment, and delayed progression across multiple conditions (specific intervention outcomes truncated). The synthesis is clinically significant for designing integrated care pathways that address multimorbidity rather than single diseases.
Valabhji J, Hope D, Sayed NE et al. · Lancet (London, England) · (2026) · 2 citations · View on PubMed ↗
Orforglipron compared with dapagliflozin in adults with type 2 diabetes and inadequate glycaemic control with metformin (ACHIEVE-2): a multicentre, randomised, non-inferiority, open-label, phase 3 trial.
This phase 3, multicentre, randomised, non-inferiority, open-label (orforglipron dose-blinded) trial compared orforglipron, an oral non-peptide GLP-1 receptor agonist, with dapagliflozin, an oral SGLT2 inhibitor, in adults with type 2 diabetes inadequately controlled on metformin. It enrolled adults with HbA1c 7.0%–10.5% and assessed efficacy and safety over 40 weeks across 73 sites in six countries (primary endpoint results truncated in the abstract). If orforglipron is non-inferior with acceptable safety, it would support orforglipron as an oral alternative to SGLT2 inhibition for combination therapy in metformin-treated type 2 diabetes.
Welch M, Forst T, Jia W et al. · Lancet (London, England) · (2026) · View on PubMed ↗
Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with obesity or overweight (VISTA): a multicentre, phase 2, randomised, placebo-controlled clinical trial.
This phase 2, double-blind, randomized, placebo-controlled dose-ranging trial studied the oral small-molecule GLP-1 receptor agonist elecoglipron (AZD5004) in adults with obesity or overweight and at least one weight-related condition without diabetes. Over 36 weeks, elecoglipron was evaluated for efficacy, safety, and tolerability versus placebo (with once-daily dosing without food/fluid restriction). If effective and well tolerated, elecoglipron could provide an oral alternative to injectable GLP-1 therapies for weight management in people with obesity/overweight and related comorbidities.
Davies MJ, Aroda VR, Rosenstock J et al. · Lancet (London, England) · (2026) · View on PubMed ↗ · Free PDF ↗
How Would You Manage This Patient With Iron Deficiency Anemia? Grand Rounds Discussion From Beth Israel Deaconess Medical Center.
This Grand Rounds discussion reviewed evidence-based management of iron deficiency anemia (IDA), emphasizing diagnosis and treatment considerations in common clinical scenarios. It highlighted that iron deficiency can occur with or without anemia and that reliance on hemoglobin thresholds may miss ID in menstruating women, alongside practical diagnostic steps using iron indices such as ferritin and transferrin saturation. The significance is improved clinical recognition and management of IDA to prevent morbidity from underdiagnosis and undertreatment.
Cool JA, Martens KL, Freed JA et al. · Annals of internal medicine · (2026) · View on PubMed ↗
Continuing Glucagon-Like Peptide-1 Receptor Agonists Into the First Trimester of Pregnancy and Pregnancy Outcomes : A Target Trial Emulation Study Using Claims Information.
This target trial emulation study used U.S. insurance claims (Merative MarketScan, 2011–2024) to estimate pregnancy risks associated with continuing glucagon-like peptide-1 receptor agonists (GLP-1RAs) into the first trimester. Among pregnant women aged 16–55 with GLP-1RA dispensing in the 90 days before last menstrual period, continuation into the first trimester (≥1 further dispensation) was compared with noncontinuation for outcomes including nonlive birth, abnormal fetal growth, and major congenital malformation (MCM). The findings provide clinically relevant safety evidence for early-pregnancy GLP-1RA exposure to inform counseling and prescribing decisions.
Brown JP, Huybrechts KF, Straub L et al. · Annals of internal medicine · (2026) · View on PubMed ↗
KRAS Inhibitor Induced Cancer Cell Death Enhances Sensitivity to Immune-Mediated Bystander Killing of Drug-Resistant Subclones.
This preclinical study examined how KRAS inhibitor–induced cancer cell death affects immune-mediated killing of drug-resistant subclones in tumors containing minor resistant populations. In models of KRAS-G12C inhibitor resistance, treatment with G12Ci (e.g., adagrasib and RMC-4998) drove rapid outgrowth of resistant cells, but combining G12Ci with immune-enhancing therapies improved sensitivity to bystander killing of drug-resistant subclones. The work supports combination strategies that couple KRAS-G12C targeting with immune activation to limit resistance-driven relapse.
Tomaschko M, Ng K, Moore C et al. · Cancer research · (2026) · View on PubMed ↗ · Free PDF ↗
Achieving at Least 15% Weight Loss Within 2 Years of Type 2 Diabetes Diagnosis Is Associated With Lower Risks of Macrovascular and Microvascular Complications: A U.K. Cohort Study.
This U.K. cohort study evaluated whether achieving ≥15% weight loss within 2 years after type 2 diabetes diagnosis is associated with reduced subsequent macrovascular and microvascular complications. Using Clinical Practice Research Datalink Aurum linked to hospital and mortality data (2000–2024), adults with obesity and type 2 diabetes who achieved ≥15% weight loss were propensity score matched 1:4 to controls with stable weight (<2% change), and time-to-first complication outcomes were compared. The results support early, clinically meaningful weight loss as a strategy to lower long-term vascular complication risk after diagnosis.
Johnsen E, Bengtsson J, Halasa T et al. · Diabetes care · (2026) · View on PubMed ↗ · Free PDF ↗
Infectious disease & host–pathogen interactions
PFN1 inhibits lytic replication of Kaposi sarcoma-associated herpesvirus through SQSTM1/p62-mediated selective autophagy targeting the KSHV helicase.
The study investigated how PFN1 (profilin 1) restricts Kaposi sarcoma-associated herpesvirus (KSHV) lytic replication, focusing on SQSTM1/p62-mediated selective autophagy targeting the viral helicase ORF44. PFN1 inhibited KSHV lytic replication by promoting autophagy-lysosomal degradation of ORF44, with mechanistic data showing PFN1 interaction with ORF44 and enhanced polyubiquitination of PFN1 involving the E3 ubiquitin ligase TRIM37. This identifies a host autophagy pathway (PFN1–SQSTM1/p62) as a potential antiviral strategy against KSHV-driven malignancies.
Sun X, Dong J, Liang X et al. · Autophagy · (2026) · View on PubMed ↗
Dietary tryptophan supplementation prevents sepsis by enhancing macrophage bacterial defense through GPR37 activation.
This study tested whether dietary L-tryptophan supplementation and its metabolite indole-3-pyruvate (IPyA) prevent sepsis in a mouse septic model by enhancing macrophage bacterial defense through GPR37 activation. The authors found improved survival and reduced organ injury and bacterial burden, alongside increased macrophage antimicrobial activity mediated by GPR37 signaling. These results support a host-microbe metabolite–receptor mechanism that could be leveraged to develop adjunct therapies for sepsis.
Xie S, Lyu F, Gao K et al. · Chinese medical journal · (2026) · View on PubMed ↗ · Free PDF ↗
Mycobacterium tuberculosis IDH-PPARγ interaction suppresses GPX4 to drive macrophage ferroptosis and sustain persistent infection.
This mechanistic study investigated how Mycobacterium tuberculosis (M.tb) manipulates host macrophage ferroptosis during infection, focusing on the M.tb isocitrate dehydrogenase (IDH)–PPARγ axis. Using single-cell RNA sequencing and proteomics, the authors found that M.tb infection upregulated PPARγ in macrophages via an IDH–PPARγ interaction that impaired PPARγ proteasomal degradation, leading to suppression of glutathione peroxidase 4 (GPX4) and promotion of macrophage ferroptosis. By linking a specific bacterial enzyme–host nuclear receptor interaction to ferroptosis control, the work identifies a potential target pathway to disrupt persistent M.tb infection.
Pu W, Zhang X, Tian M et al. · Nature communications · (2026) · View on PubMed ↗ · Free PDF ↗
Widespread circulation of Alongshan virus in Austria and serological evidence for infection in humans: a nationwide molecular and serological observational study.
This nationwide molecular and serological observational study investigated Alongshan virus circulation in Austria by combining PCR-based tick surveillance with serological and molecular screening of individuals with suspected tick-borne encephalitis or tick exposure. It aimed to characterize the temporal and geographic distribution of Alongshan virus across Austria using tick-derived and human infection evidence (specific results truncated in the abstract). Demonstrating widespread circulation and human serological evidence would strengthen the case for Alongshan virus as a relevant zoonotic pathogen in Europe and inform surveillance and diagnostic considerations.
Florian DM, Jetzinger P, Schötta AM et al. · The Lancet. Microbe · (2027) · View on PubMed ↗ · Free PDF ↗
mRNA delivery of a class 1/4 SARS-CoV-2 neutralizing antibody protects against diverse sarbecoviruses in a lethal mouse challenge model.
The study developed and evaluated mRNA-delivered class 1/4 SARS-CoV-2 neutralizing antibodies in a lethal mouse challenge model against diverse sarbecoviruses. The mRNA antibody delivery protected mice from lethal challenge with multiple sarbecoviruses, leveraging broadly targeted RBD epitopes derived from a patient-derived bNAb lineage. This supports mRNA antibody therapeutics as a rapid, adaptable countermeasure against antigenically drifted SARS-related viruses and future zoonotic spillovers.
Skelly AN, Fan C, Keeffe JR et al. · Proceedings of the National Academy of Sciences of the United States of America · (2026) · View on PubMed ↗ · Free PDF ↗
Generated automatically on June 10, 2026 from PubMed’s trending articles. Summaries are AI-generated; always consult the original publication for clinical or research decisions.