ATP7A (ATPase Copper Transporting Alpha)

MKV3's ability to potentiate copper-mediated killing in multidrug-resistant bacterial pathogens highlights its potential as an antimicrobial adjuvant, while its attenuation of mammalian ATP7A/B function offers promise in oncology and copper-related diseases. Collectively, these findings establish a new tool for targeting of Cu + -ATPases with wide-ranging applications across biological systems.

In vivo, DCTH showed enhanced tumor targeting, effective photothermal response, significant tumor growth inhibition, immunogenic cell death (ICD) induction, dendritic cell maturation, and increased cytotoxic T-cell infiltration. Overall, DCTH presents a modular and intelligent nanotherapeutic platform leveraging metal-gas synergy to overcome TME-associated therapeutic resistance and achieve multimodal antitumor therapy.

Future directions include integrating multi-omics approaches to identify novel therapeutic targets and developing combination therapies to overcome hypoxia-induced resistance. This review provides a comprehensive overview of copper metabolism in cancer, emphasizing the potential of cuproptosis induction as a powerful strategy for oncologic intervention.

Targeting the circadian clock or fatty acid desaturation augmented cuproptosis antitumor effects. Crosstalk between the core circadian clock and copper sustains GSCs, reshaping fatty acid metabolism and promoting drug resistance, which may inform development of combination therapies for GBM.

Thus, GATOR1 not only participates in the cellular response to amino acid availability but also plays a role in resistance to DNA-damaging anticancer drugs. This novel function of GATOR1 should be taken into account when developing new strategies to combat chemoresistance.

Temozolomide (TMZ) remains the standard chemotherapy; however, its effectiveness is often hindered by the development of acquired resistance... Our findings indicate that TMZ and copper synergistically induce cuproptosis in GBM by disrupting the TRIM14-ATP7A regulatory axis and promoting intracellular copper accumulation. Targeting TRIM14 or ATP7A to enhance cuproptosis may represent a promising therapeutic strategy to overcome TMZ resistance and improve clinical outcomes in GBM patients.

State-of-the-art synchrotron X-ray fluorescence studies demonstrated that Cuphoralix alters the subcellular copper distribution, redistributing it from the vesicles to the cytosol. This redistribution likely accounts for the potent cytotoxicity of this novel class of Cu(I) ionophores, supporting further studies on their anticancer potential.

As a result, complete elimination of primary and distant tumors in mice was achieved at low doses without side effects. The US-sensitized cuproptosis switch may provide opportunities for elimination of local residual tumors and abscopal metastatic foci for final tumor eradication.

Herein, a novel MIIT initiator, layered double hydroxides composite, disulfiram (DSF)-loaded ZnCuAl-LDH, was constructed to efficiently co-deliver multiple metal ions and enhance the retention ability of metal ions within the cells...Therefore, ZCA-LDH@DSF demonstrated a remarkable ability to induce MIIT, thereby triggering multiple programs of cell death and inhibiting tumor growth and metastasis. Overall, the good biological safety and application prospect of ZCA-LDH@DSF initiator provide a new treatment model for combating tumor.

To improve the permeability across blood-brain tumor barrier (BTB), minoxidil sulfate (MS) and T7 peptide are modified on Cu-OME SNDs to produce Cu-OME/MS@T7 SNDs. Meanwhile, the released OME further blocks copper efflux by suppressing ATP7A copper efflux transporter. Collectively, this work demonstrates the effectiveness of OME-mediated copper delivery in inducing copper dyshomeostasis and triggering cuproptosis, highlighting a promising therapeutic approach through synchronous remodeling of copper influx and efflux.

This further supports the inhibitory effect of thymol on cuproptosis, which underlies its protective properties. This study illustrates that cuproptosis and oxidative stress play crucial roles in the development and progression of cisplatin-induced nephrotoxicity, and the protective activity of thymol is attributed, at least in part, to blunting these mechanisms.

Furthermore, when challenged with identical intracellular oxaliplatin levels, AsPC‑1 cells exhibited delayed caspase 3/7 activity initiation, weaker induction of pro‑apoptotic genes BBC3 (1.7‑fold vs. 5‑fold) and PMAIP (2.5‑fold vs. 6‑fold), but stronger enhancement of anti‑apoptotic Jun expression (7‑fold vs. 3‑fold) than BxPC‑3 cells. Taken together, oxaliplatin resistance in PDAC models may be highly linked to a poor apoptotic response, whereas drug uptake seems to be of minor relevance.