Papers & Updates

This review addresses the critical challenge of sequencing antibody-drug conjugates (ADCs) in advanced gastric cancer after disease progression, a gap in current guidelines. It synthesizes the biology of ADC cross-resistance, analyzes target switching dynamics (e.g., HER2 to CLDN18.2) and the role of re-biopsy/ctDNA for monitoring. The paper proposes a three-pillar decision-making framework, integrating cross-resistance risk, target landscape reassessment, and shared decision-making, to guide clinical practice until prospective trials establish evidence-based strategies.

This research introduces a deep learning framework combining Cu-Cyto, an image cytometry platform for detecting approximately twenty cell types from immunohistochemistry-stained whole-slide images, with the Co-Localization Index to quantify spatial interactions between two or three cell types. Applied to rectal cancer, this framework revealed that stromal, but not intratumoral, CD103⁺CD8⁺ T cell density independently predicts relapse-free survival, demonstrating the critical importance of spatial relationships in understanding the tumor immune microenvironment beyond simple cell counts.

Using a novel chemical genetics strategy (CG-SLENP), this study uncovered that PROTACs preferentially degrade pre-existing proteins over newly synthesized ones, revealing protein age as a critical determinant of degradation efficacy. This age-dependent bias explains incomplete target clearance and rebound kinetics, establishing protein maturation state as an important consideration for future degrader design and evaluation.

This phase 1 study evaluated TAK-102, a novel GPC3-targeted CAR T-cell therapy engineered to co-express IL-7 and CCL19, in 11 patients with advanced solid tumors. The treatment exhibited a manageable safety profile with no dose-limiting toxicities, and while no objective responses were observed, 45.5% of patients achieved stable disease, showing early evidence of biological activity such as dose-dependent expansion and increased tumor infiltration by CD8+ T cells.

This research reports a general stereoselective platform for synthesizing chiral or meso 1,2,3,4-tetrasubstituted bicyclo[1.1.0]butanes (BCBs) from internal alkynes and triftosylhydrazone-derived carbenes. The method exploits a chiral dirhodium catalyst, Rh2(R-3,5-diPheTPCP)4, which enables exquisite enantioselective discrimination and high enantioenrichment of polysubstituted BCBs via kinetic resolution of cyclopropene intermediates.

This study developed charge-mixed nanogels to overcome the efficacy-toxicity trade-off of cationic nanocarriers for siRNA delivery. Through systematic optimization of charge composition, size, and cross-linking, an optimal formulation (80% cationic, 20% anionic, 83 nm, 20% disulfide cross-linked) was identified that achieved potent gene silencing (83%) and antitumor efficacy (84.3%) with significantly reduced toxicity, primarily by diluting the positive charge density while enabling glutathione-responsive release.

This study repurposed griseofulvin (GF) as a dual-action agent for glioblastoma, demonstrating its ability to both inhibit tumor growth via G2/M arrest and enhance 5-aminolevulinic acid (5-ALA)-mediated photodynamic diagnosis (PDD) by increasing protoporphyrin IX (PpIX) accumulation through ferrochelatase regulation. Through in vitro and orthotopic mouse models, GF significantly reduced tumor growth and improved tumor visualization with a higher tumor-to-normal PpIX fluorescence ratio, identifying it as a promising candidate for glioblastoma treatment and enhanced surgical guidance.

This research presents a modular "inverse vaccine" platform using anionic liposomes that encapsulate a dexamethasone-conjugated, disease-specific peptide antigen. In murine models of arthritis and experimental autoimmune encephalomyelitis, this platform significantly suppressed disease progression, reduced joint damage, and shifted immune responses away from pathogenic Th17 cells. These findings highlight a promising, antigen-specific tolerogenic therapeutic strategy for autoimmune diseases.

This study utilized patient-derived bladder cancer models and human cohorts to demonstrate that gemcitabine-cisplatin (GC) chemotherapy induces downregulation of the enfortumab vedotin (EV) target, Nectin-4, leading to EV resistance in GC-resistant cells. This Nectin-4 loss is linked to an epithelial-to-mesenchymal transition (EMT)-like transcriptional shift, suggesting the importance of Nectin-4 assessment before EV therapy in post-platinum settings and highlighting alternative druggable vulnerabilities like the TGF-beta pathway in resistant tumors.

Addressing the significant challenges of aggressive pancreatic cancer and its resistance to conventional therapies, this research highlights poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) as a promising targeted drug delivery strategy. PLGA NPs facilitate controlled drug release, enhanced bioavailability, and reduced off-target effects by encapsulating diverse therapeutic agents and can be functionalized to overcome tumor microenvironment barriers and improve treatment outcomes.

This review systematically examines photothermal dry reforming of methane (DRM), a solar-driven strategy converting CH4 and CO2 into syngas by leveraging both localized heating and energetic charge carriers from photons. It delves into fundamental mechanisms and summarizes recent advances in plasmonic metal and metal-semiconductor hybrid catalysts, emphasizing their structure-activity-stability relationships. The paper concludes by discussing key challenges and future opportunities in this field.

Researchers synthesized poly(L-ornithine) (PLO) derivatives with varying cyclobutyl hydrophobic modifications to develop stable antimicrobial peptide mimetics for peritonitis therapy. They identified PLO(20%) as the optimal compound, demonstrating robust, membrane-disrupting antibacterial activity against MRSA (including biofilm eradication) that was unaffected by harsh environmental conditions. In a mouse peritonitis model, PLO(20%) effectively reduced bacterial burdens and improved survival without toxicity, highlighting hydrophobic modification of PLO as a promising strategy for treating complex infections.

This study investigated the antimicrobial potential of *Trametes versicolor* extracts against clinically isolated pathogens, optimizing cultivation and extracting with different solvents. Methanol extracts demonstrated the highest overall inhibition, notably against *S. aureus*, with phytochemical analysis identifying terpenoid and oxygenated constituents. Integrated in silico analyses, including molecular docking to *S. aureus* DNA gyrase B and molecular dynamics simulations, identified specific ligands (e.g., CID 5281515) with promising binding affinities, suggesting their potential as antimicrobial lead compounds.

This study investigated the anticancer properties of the *S*- (E1) and *R*-enantiomers (E2) of reduced Mebendazole using in vitro assays, secretome profiling, and RNA sequencing in breast cancer cells. It found that E1 was the more biologically active enantiomer, exhibiting preferential toxicity to tumor cells, modulating cell cycle, apoptosis, β-tubulin levels, and migration, with a distinct molecular response involving HER2/HER3 and hypoxia pathways. These findings suggest that E1, the *S*-enantiomer, is a promising anticancer candidate due to its retained activity, tumor selectivity, and unique molecular profile.

This paper reviews significant advances in targeted therapies for advanced non-small-cell lung cancer (NSCLC), summarizing established alterations (e.g., EGFR, ALK) and emerging biomarkers. It highlights how newer generations of tyrosine kinase inhibitors, bispecific antibodies, and antibody-drug conjugates improve outcomes and intracranial disease control. The research emphasizes that addressing acquired resistance and guiding complex individualized treatments requires repeat molecular profiling and adaptive strategies, underscoring the need for comprehensive profiling and equitable access for future progress.

This review introduces membrane and extracellular targeted protein degradation (meTPD) as a strategy to degrade previously inaccessible extracellular and membrane-associated proteins, surpassing limitations of intracellular degradation methods. It categorizes diverse meTPD approaches by their trafficking and degradation routes, such as lysosome-targeting or transmembrane E3 ligase recruitment. The paper also details critical molecular design parameters—including ligand affinity, linker architecture, and valency—essential for productive degradation and advancing these modalities towards predictable therapeutic applications.

Observing delayed skin wound healing in colitis, researchers developed AHR-responsive carbon dots that significantly alleviated colitis and accelerated impaired skin wound healing. These carbon dots achieved this by activating AHR to induce Treg cells, which then produced CCL1 to enhance macrophage efferocytosis via STAT3-SCARB1 signaling, thereby establishing a pro-regenerative immune microenvironment in both the colon and skin wounds.

This replication study investigates the repurposing of three drugs for Parkinson's Disease prevention, using data from French healthcare databases.

Researchers engineered programmable DNA nanostructures (2D triangles or 3D tetrahedrons) to multivalently display Tankyrase-binding peptides (TBP), targeting Tankyrase's substrate binding domains to inhibit the Wnt/β-catenin pathway, a common cancer pathway. These nanostructures efficiently delivered TBP into cells and significantly downregulated Wnt signaling, unlike free TBP, establishing them as a modular platform for the multivalent inhibition of clustered intracellular protein targets.

Metal nanoparticles (NPs) offer a multi-target strategy against antimicrobial resistance (AMR) by disrupting bacterial membranes, inducing oxidative stress, and crucially, modulating bacterial gene expression to suppress resistance mechanisms like efflux pumps and biofilm formation. Advanced functionalization techniques enhance their efficacy and specificity for targeted delivery, showing promise in applications such as antimicrobial coatings and wound dressings, although challenges like cytotoxicity and pharmacokinetics must be addressed for clinical translation.