Targets

Small extracellular vesicles (sEVs) are pivotal mediators of intercellular epigenetic communication in cancer. Following MISEV2023, we use the size- and isolation-based term sEV throughout, because most primary studies cited here cannot resolve which biogenetic route generated the vesicles they analyzed. By selectively packaging and transferring noncoding RNAs (ncRNAs), DNA fragments, chromatin-modifying enzymes, and metabolic effectors, sEVs reprogram recipient-cell chromatin architecture without altering the underlying DNA sequence. Tumor-derived sEVs engage stromal, immune, and vascular compartments to drive malignant progression through mechanisms that include miRNA-directed suppression of DNA methyltransferases (DNMTs), lncRNA-scaffolded Polycomb Repressive Complex 2 (PRC2) recruitment, depositing H3K27me3, and oncometabolite-mediated inhibition of TET dioxygenases. This narrative review synthesizes mechanistic, preclinical, and translational evidence on sEV-driven epigenetic regulation in cancer, applies a four-level evidence hierarchy to calibrate mechanistic claims, and critically evaluates how distinct cargo classes–microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), DNMTs, and histone-modifying enzymes–contribute to chromatin remodeling, aberrant DNA methylation, acquired therapy resistance, and immune evasion in recipient cells. We further examine sEV cargo signatures as minimally invasive liquid biopsy biomarkers and appraise engineered sEV platforms for the precision delivery of miRNA mimics, siRNAs, and small-molecule epigenetic inhibitors. Key methodological challenges, EV isolation standardization, MISEV2023 compliance, cargo stoichiometry at physiological concentrations, in vivo biodistribution, and the transition from post-transcriptional regulation to durable chromatin-state change are critically evaluated, and a translational roadmap is proposed to guide reproducible clinical implementation of sEV-mediated epigenetic cancer therapeutics.

Metal-graphitic nanocapsules are an emerging class of metal-graphitic hybrid nanomaterials, typically consisting of a metal core confined within a single- or few-layer graphitic shell. This unique core–shell architecture integrates the tunable physicochemical properties of metal nanomaterials with the chemical stability, Raman activity, fluorescence-quenching capability, and surface functionalization capacity of graphitic materials. In particular, the metal core can provide plasmonic enhancement as well as magnetic or catalytic auxiliary functions, while the chemically protective graphitic shell protects the core from harsh environments and provides intrinsic Raman bands that can serve as internal standards under well-controlled conditions. These features make metal-graphitic nanocapsules highly attractive as robust nanoprobes for molecular spectroscopy-based chemical analysis, biosensing, and targeted diagnosis. In this review, we first summarize the synthesis strategies, formation mechanisms, and key properties of representative metal-graphitic nanocapsules. We then discuss recent advances in their use across representative analytical and biomedical scenarios, with emphasis on the integration of spectroscopic readouts with targeted recognition strategies. Particular attention is given to how the metal core and graphitic shell cooperatively enhance signal generation, molecular enrichment, selective recognition, environmental stability, internal calibration, and reliable in situ diagnosis in real samples and living systems. Finally, we discuss current challenges and future perspectives for developing metal-graphitic nanocapsules as versatile platforms for molecular spectroscopy-based analysis and diagnosis.

Acute myeloid leukemia (AML) harboring KMT2A rearrangements (KMT2A-r) accounts for approximately 5–10% of newly diagnosed cases and represents a high-risk AML subtype associated with poor clinical outcomes despite intensive treatment strategies, including allogeneic hematopoietic stem cell transplantation (HSCT). KMT2A-r AML is also characterized by a higher incidence of extramedullary disease compared with other AML subtypes. Therapeutic options for patients with relapsed/refractory (R/R) disease, particularly after post-HSCT relapse, remain extremely limited. In recent years, menin inhibitors have emerged as a promising targeted therapeutic class for KMT2A-r and NPM1-mutated AML by disrupting the aberrant HOX/MEIS1 transcriptional program. Revumenib, a first-in-class menin inhibitor, has shown encouraging efficacy in early-phase clinical trials. Other menin inhibitors, including ziftomenib, bleximenib, and enzomenib, have also demonstrated clinical activity, with distinct pharmacokinetic, pharmacodynamic, and safety profiles. We report the case of a 36-year-old patient with KMT2A-r AML who relapsed after HSCT with both bone marrow and hepatic involvement. Compassionate-use treatment with revumenib (160 mg twice daily on days 1–28 of each 28-day cycle) induced, after two treatment cycles, complete hematologic remission with no detectable abnormal myeloid blast population by multiparameter flow cytometry (MFC) and complete radiological resolution of hepatic lesions. However, despite prior intrathecal CNS-directed therapy and sustained systemic disease control, the patient subsequently developed an isolated central nervous system (CNS) relapse. This case highlights a potential discordance between systemic and CNS disease control during menin inhibitor therapy and emphasizes the need for further investigation into CNS surveillance and disease management in patients achieving deep systemic responses.