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DropVLA: An Action-Level Backdoor Attack on Vision-Language-Action Models
MedCollab: IBIS-Guided Multi-Agent Collaboration with Hierarchical Disease Relation Chains for Clinical Diagnosis
Hepatic Usp2 orchestrates de novo lipogenesis through G3bp2 stabilization and β-catenin activation
Cell Death Discovery, Published online: 14 September 2026; doi:10.1038/s41420-026-03333-2
Hepatic Usp2 orchestrates de novo lipogenesis through G3bp2 stabilization and β-catenin activationDense RNA motif modifications enable robust in vivo prime editing and enhance efficiencies of diverse editing systems
Nature Biomedical Engineering, Published online: 11 September 2026; doi:10.1038/s41551-026-01787-4
Applying extensive chemical modifications to RNA motifs substantially enhances prime editing efficiency in vivo and can be applied for improved efficiencies across RNA-based editing systems.NBR1-Mediated Autophagic Degradation of YTHDF1 Curtails <em>FDX1</em> Translation to Drive Concurrent Multikinase Inhibitor Resistance and Cuproptosis Tolerance
Cancer Commun (Lond). 2026 Sep 11;46:0048. doi: 10.34133/cancomm.0048. eCollection 2026.
ABSTRACT
Background: Cancer cells frequently acquire adaptive resistance to targeted therapies; however, strategies capable of concurrently overcoming treatment tolerance and reactivating cell death pathways are currently lacking. Here, we investigated the dual role of ferredoxin 1 (FDX1) in modulating both multikinase inhibitor (MKI) sensitivity and cuproptosis susceptibility in hepatocellular carcinoma (HCC), and sought to develop a therapeutic approach for reversing resistance. Methods: HCC models, both in vitro and in vivo, were employed to investigate the role of FDX1 in MKI resistance and cuproptosis evasion. Polysome profiling, SunTag translation reporters, CRISPR-Cas9 mutagenesis, and mass spectrometry were employed to delineate the underlying mechanisms. A codelivery nanoliposome system was engineered and tested in orthotopic HCC models. Results: Prolonged exposure to MKIs led to the down-regulation of FDX1 protein levels, resulting in MKI resistance and cuproptosis tolerance in HCC both in vitro and in vivo. Mechanistically, we found that MKIs inactivated protein kinase B (PKB, also known as AKT)-mechanistic target of rapamycin (mTOR) signaling, thereby suppressing the SET and MYND domain-containing protein 2 (SMYD2)-mediated methylation of YTH domain family protein 1 (YTHDF1) at lysine 515 (K515). Hypomethylated YTHDF1 was degraded via next to BRCA1 gene 1 protein (NBR1)-dependent autophagy, leading to the repression of N6-methyladenosine modification-dependent translation of FDX1 mRNA. FDX1 deficiency drove MKI resistance by reactivating AKT survival signaling while impairing cuproptosis through reduced divalent copper ions (Cu2+) to monovalent copper ions (Cu+) conversion and the loss of protein lipoylation. Additionally, restoring FDX1 expression through NBR1 knockdown or YTHDF1 overexpression overcame MKI resistance and resensitized HCC cells to cuproptosis. Finally, a nanoliposomal system, super cuproptosis detonator liposome, designed for the codelivery of NBR1 small interfering RNA, a copper ionophore, and sorafenib restored FDX1-dependent cuproptosis and exhibited marked anti-HCC efficacy, suppressing HCC growth in vivo. Conclusions: MKIs suppressed SMYD2-mediated YTHDF1 methylation at K515 via the inactivation of AKT-mTOR signaling. This led to the inhibition of FDX1 translation, resulting in AKT signaling reactivation and protein lipoylation impairment, effects that contributed to both MKI resistance and cuproptosis tolerance in HCC. Overcoming MKI resistance and resensitizing cells to cuproptosis by targeting NBR1-mediated YTHDF1 degradation using a nanoliposomal codelivery system represents a promising strategy for HCC treatment.
PMID:42729649 | PMC:PMC13562797 | DOI:10.34133/cancomm.0048
Modality-Decoupled Federated Learning for Privacy-Preserving Embodied Intelligence in 6G
MADS: Multi-Agent Dialogue Simulation for Diverse Persuasion Data Generation
Early stage nonsmall cell lung cancer: Toward a risk-adaptive paradigm in the era of biologic precision
CA Cancer J Clin. 2026 Sep-Oct;76(5):e70100. doi: 10.3322/caac.70100.
ABSTRACT
The clinical landscape of early stage nonsmall cell lung cancer is at transformative crossroads. Driven by the widespread adoption of low-dose computed tomography screening, the frequent detection of ground-glass opacities, and a rising incidence among never-smokers, the diagnostic center of gravity has shifted toward earlier, potentially curable disease. This shift has been accompanied by equally important therapeutic advances, including parenchyma-sparing surgical techniques, minimally invasive platforms enhanced by digital navigation, and the transformative integration of perioperative immunotherapy and targeted agents. Concurrently, noninvasive monitoring approaches, such as liquid biopsy, have emerged as powerful tools to guide precision management. Despite this progress, substantial barriers to achieving a universal cure persist. Clinicians continue to face uncertainty in the management of ground-glass opacities, the anatomy-based TNM staging system fails to capture the biologic heterogeneity of early tumors, and global disparities in access to innovation remain unresolved. To address these challenges, the authors propose a shift toward a risk-adaptive management paradigm that harnesses artificial intelligence-driven analytics and multi-omics profiling to tailor treatment intensity according to each patient's biologic risk. Such an approach would enable appropriate escalation for high-risk individuals while permitting safe de-escalation for those at low risk. This holistic, lifespan-oriented strategy must be embraced to deliver equitable and durable cures for patients with early stage nonsmall cell lung cancer.
PMID:42713910 | PMC:PMC13555834 | DOI:10.3322/caac.70100
Targeting KRAS reprograms a Treg-dominant immunosuppressive microenvironment and sensitizes KRAS-mutant gastric adenocarcinoma to CTLA-4 immunotherapy
Sci China Life Sci. 2026 Sep 3. doi: 10.1007/s11427-026-3438-4. Online ahead of print.
ABSTRACT
Oncogenic KRAS mutations define a distinct molecular subset of gastric adenocarcinoma (GA), yet their impact on the tumor immune microenvironment remains incompletely understood. In this study, we established a genetically faithful and immunocompetent KRASG12D-driven mouse model of GA, together with matched organoids and cell lines, to investigate how oncogenic KRAS shapes tumor-immune interactions. KRAS-mutant tumors consistently developed an immunosuppressive microenvironment characterized by enrichment of regulatory T cells (Tregs), accompanied by reduced cytotoxic lymphocyte infiltration and intrinsic resistance to PD-1 blockade. Although pharmacologic targeting of KRAS effectively suppressed tumor growth and increased immune cell infiltration, functional immune analyses revealed persistent Treg-mediated immunosuppression that limited effective antitumor immunity. Mechanistically, TGF-β signaling was required to maintain Treg dominance and suppress effector T cell function in KRAS-driven tumors. Importantly, disruption of this suppressive axis through combined KRAS inhibition and CTLA-4 blockade attenuated TGF-β activity, impaired Treg function, and enhanced antitumor immune responses in vivo. Collectively, these findings identify oncogenic KRAS as a key regulator of TGF-β-dependent immune suppression in GA and provide mechanistic insight into immune evasion within this molecular subtype.
PMID:42714795 | DOI:10.1007/s11427-026-3438-4
Early stage nonsmall cell lung cancer: Toward a risk-adaptive paradigm in the era of biologic precision
CA Cancer J Clin. 2026 Sep-Oct;76(5):e70100. doi: 10.3322/caac.70100.
ABSTRACT
The clinical landscape of early stage nonsmall cell lung cancer is at transformative crossroads. Driven by the widespread adoption of low-dose computed tomography screening, the frequent detection of ground-glass opacities, and a rising incidence among never-smokers, the diagnostic center of gravity has shifted toward earlier, potentially curable disease. This shift has been accompanied by equally important therapeutic advances, including parenchyma-sparing surgical techniques, minimally invasive platforms enhanced by digital navigation, and the transformative integration of perioperative immunotherapy and targeted agents. Concurrently, noninvasive monitoring approaches, such as liquid biopsy, have emerged as powerful tools to guide precision management. Despite this progress, substantial barriers to achieving a universal cure persist. Clinicians continue to face uncertainty in the management of ground-glass opacities, the anatomy-based TNM staging system fails to capture the biologic heterogeneity of early tumors, and global disparities in access to innovation remain unresolved. To address these challenges, the authors propose a shift toward a risk-adaptive management paradigm that harnesses artificial intelligence-driven analytics and multi-omics profiling to tailor treatment intensity according to each patient's biologic risk. Such an approach would enable appropriate escalation for high-risk individuals while permitting safe de-escalation for those at low risk. This holistic, lifespan-oriented strategy must be embraced to deliver equitable and durable cures for patients with early stage nonsmall cell lung cancer.
PMID:42713910 | DOI:10.3322/caac.70100
Multi-Omics Biomarker Signatures for Precision Diagnosis and Prognosis in Primary Liver Cancer: A Literature Review
Biofactors. 2026 Sep-Oct;52(5):e70136. doi: 10.1002/biof.70136.
ABSTRACT
Primary liver cancer (PLC) is a biologically heterogeneous group of malignancies dominated by hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and a smaller subset of combined hepatocellular-cholangiocarcinoma (cHCC-CCA), and its clinical burden remains high because current diagnostic and prognostic tools do not adequately capture molecular diversity. Conventional imaging, serum markers, and histopathological assessment remain insufficient for precise early diagnosis, subtype-resolved classification, and outcome stratification, while tissue and liquid biopsy approaches have expanded the range of analytes available for clinical assessment. Recent studies have identified candidate biomarker signatures across genomic, epigenomic, transcriptomic, proteomic, metabolomic, and circulating layers, suggesting that integrated multi-omics profiling may better represent tumor lineage, clonal evolution, immune context, and therapeutic vulnerability than isolated molecular readouts. However, these layers are not equally mature for clinical use: genomic testing is closest to routine therapeutic application in iCCA, plasma methylation assays are advancing for HCC surveillance augmentation, and many proteomic or metabolomic panels remain validation-stage tools. Their clinical value remains constrained by sampling bias, biospecimen-dependent signal loss, assay standardization, cost, and the need for prospective validation across clinically diverse populations. This narrative review critically synthesizes current evidence on multi-omics biomarker signatures for precision diagnosis and prognosis in primary liver cancer and argues that clinically useful signatures should be question-specific, stage-aware, and specimen-aware rather than universal multi-analyte panels.
PMID:42697859 | PMC:PMC13545153 | DOI:10.1002/biof.70136
CAFs shape the immunosuppressive microenvironment of pancreatic cancer through the Lin28b-STING Axis
Nat Commun. 2026 Aug 7;17(1):9491. doi: 10.1038/s41467-026-76495-3.
ABSTRACT
Cancer-associated fibroblasts comprise diverse functionally distinct cellular subsets, with certain subpopulations exerting pivotal influence in shaping the pancreatic cancer immune microenvironment. Here we show that Lin28b+ cancer-associated fibroblasts contribute to establishing an immunologically cold tumor microenvironment in pancreatic ductal adenocarcinoma. Mechanistically, Lin28b directly binds to STING mRNA and promotes its degradation, thereby suppressing STING expression and downstream type I interferon signaling. Loss of Lin28b in cancer-associated fibroblasts activates the cGAS-STING-interferon signaling cascade, enhancing dendritic cell antigen presentation and CD8+ T cell cytotoxic function. Importantly, genetic inhibition of Lin28b in cancer-associated fibroblasts enhances sensitivity to anti-PD-L1 immune checkpoint blockade therapy. These findings reveal that targeting the Lin28b-STING axis represents a promising therapeutic strategy for overcoming the intrinsic resistance of pancreatic ductal adenocarcinoma to immunotherapy.
PMID:42693143 | PMC:PMC13542369 | DOI:10.1038/s41467-026-76495-3
Disruption of the AR/ZNF217/PROM2 axis sensitizes prostate cancer to ferroptosis and enzalutamide therapy
Oncogenesis, Published online: 11 August 2026; doi:10.1038/s41389-026-00649-7
Disruption of the AR/ZNF217/PROM2 axis sensitizes prostate cancer to ferroptosis and enzalutamide therapy