Dendritic SiO2 nanoparticles were sequentially loaded with elesclomol-copper complex (ESCu) and hemin, followed by hyaluronic acid (HA) coating to achieve CD44-mediated tumor targeting and HAase/pH-responsive drug release...In vivo results further demonstrated enhanced tumor accumulation, superior tumor growth inhibition, and favorable preliminary biosafety. This work provides a targeted nanotherapeutic strategy for enhanced cancer treatment through cuproptosis-photothermal combination therapy.

Notably, combining the SIRT5 inhibitor MC3482 with the cuproptosis inducer Elesclomol-Cu synergistically suppresses tumor growth in vivo, suggesting a promising therapeutic strategy. These findings elucidate mechanisms underlying cuproptosis resistance and propose a novel treatment approach for LUAD.

Elesclomol (15 nM) and copper chloride (CuCl₂, 10 µM) were used to induce cuproptosis, while DLAT overexpression and S6 kinase inhibition were used to clarify signaling processes. MELK expression was considerably elevated in DLBCL tissues and cell lines (P < 0.05)...On the other hand, MELK-mediated effects on cuproptosis and intracellular copper buildup were abolished by S6K suppression or DLAT overexpression. Through the PI3K/mTOR/S6K-DLAT axis, MELK imparts resistance to cuproptosis and increases DLBCL cell survival. MELK targeting may increase copper-induced cytotoxicity, offering a possible DLBCL treatment approach.

Herein, a carrier-free GSH-responsive in situ nanoreactor (TECJ) is fabricated, of which Cu ionophore elesclomol (ES), GSH-responsive nitric oxide (NO) donor O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazin-1-yl] diazen-1-ium-1,2-diolate (JSK) and Cu2+ are integrated via self-assembly and coated with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)...Afterwards, the process above synergistically activates immunogenic cell death and cascades immunotherapy. Finally, TECJ successfully suppresses tumor growth and prevents tumor metastasis.

In patient-derived models, high HSF2/FDX1 expression predicts enhanced response to cuproptosis inducers. Our work establishes an epigenetic mechanism linking copper sensing to cuproptosis and nominates the CHD4/HSF2/FDX1 axis as potential biomarkers and therapeutic targets for precision oncology.

Furthermore, the cuproptosis activator elesclomol, inhibitor TTM, and Ras activator ML-098 were used...In vivo, 10 mg/kg Licochalcone A reduced tumor volume/weight by 42.27 ± 11.63%/45.13 ± 13.15%, with consistent protein changes (FDX1, LIAS, RAS, p-MEK and p-ERK). Collectively, it induces glioma cuproptosis via inactivating RAS/ERK, providing a potential therapeutic target.

The significantly differentially expressed genes (DEGs) from the Gene Expression Omnibus (GEO) database, which discriminate AGS and MKN45 cells in the presence of DMSO and verteporfin (a chemotherapy reagent), are determined...MKN45 was highlighted as more invasive cancer cell relative to AGS cells. PLOD2 was pointed out as a suitable target in the chemotherapy of gastric cancer.

This study identified a novel CAF-exosome-YAP-USP8-HER2 signaling axis that drives trastuzumab insensitivity in HER2-positive breast cancer. Intervening in this pathway may represent a potential treatment approach to counteract microenvironment-induced chemoresistance.

P1/2, N=19, Completed, Roswell Park Cancer Institute | Terminated --> Completed

P1/2, N=12, Not yet recruiting, Odense University Hospital

In an immune-cold syngeneic mouse PDAC model, 690 nm light activation of SM-102-containing liposomes slowed tumor growth by up to 56% and extended survival by 40%. Together, these findings suggest that integrating SM-102 into light-activated liposomes is a simple and robust strategy to enhance photochemical ICD and may improve therapeutic outcomes in immunotherapy-based combinations that utilize liposomal drug delivery systems.

We summarize opportunities and unresolved challenges in leveraging copper ionophores (e.g., elesclomol and disulfiram) and high-affinity chelators (e.g., tetrathiomolybdate) across malignant and non-neoplastic diseases. Furthermore, we address the translational challenges of precision delivery, including the use of nanoparticle-based systems to enhance therapeutic indices and the identification of biomarkers for patient stratification. By integrating recent pre-clinical and early clinical data (2023-2025), we suggest that targeting the mitochondrial-copper axis represents a promising, yet still experimentally grounded, avenue in precision medicine, while emphasizing current limitations in biomarker validation, delivery selectivity, and safety profiling.