Additionally, we found that the copper ionophore disulfiram (DSF) overcame osimertinib resistance by augmenting YTHDC2 expression. Collectively, our findings elucidate a novel YTHDC2-SLC31A1-cuproptosis axis as a key mechanism underlying EGFR-TKI resistance and propose new therapeutic strategies for its reversal.

DSF-induced autophagy may mitigate its pro-apoptotic effects, while autophagy inhibition fully blocks protein degradation pathways, leading to lethal protein accumulation. This study elucidates DSF's dual regulation of autophagy through UPS suppression and the c-Fos/beclin-1 axis, and validates the synergistic efficacy of DSF combination with CQ in CRC, providing a theoretical foundation and translational potential for DSF-based combination therapies.

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.

Addressing these limitations, we developed an innovative "4-in-1" strategy utilizing Disulfiram (DSF)-loaded Fe-based near-infrared-triggered DMTICH nanozymes integrating synergistic chemotherapy, chemodynamic therapy, photothermal therapy, and photodynamic therapy...The potent anticancer capability of DMTICH was also validated in animal studies, where it elevated the tumor site temperature to ∼58.3 °C and reduced tumor size to 12.6 % of that in the control group after a complete treatment period. This innovative approach highlights a promising synergistic "4-in-1" strategy, offering a powerful enzymatic platform for multimodal cancer therapies.

In a 4T1 TNBC mouse model, systemic [Cu(DDC)2] NP treatment significantly inhibited tumor growth without combinational chemo- or radiotherapy. This DSF-based metal-organic NP integrates drug repurposing, immune activation, and tumor microenvironment remodeling into a single platform, offering strong translational potential for treating aggressive breast cancers.

Copper chelators, such as trientine and disulfiram, can regulate intracellular copper levels and induce glioma cell death, thereby enhancing the efficacy of chemotherapy. However, the specific mechanisms of cuproptosis and its clinical application in glioma treatment require further exploration. This field of study promises to offer novel insights and directions for developing more effective glioma therapies.

These findings establish that cuproptosis exacerbates ECM pathogenesis by promoting astrocyte reactivity, highlighting copper homeostasis modulation as a potential therapeutic strategy for CM.

Despite anatomical and physiological limitations, C. elegans provides a powerful, low-cost, and translational platform for anticancer bioactive screening from medicine-food homologous materials. This strategy accelerates discovery of nutritional therapeutics and supports early cancer detection innovations.

Additionally, ferroptosis induction via radiotherapy, natural compounds (solasodine, luteolin), repurposed drugs (disulfiram/copper), or nanotechnology synergizes with immunotherapy by promoting lipid peroxidation and reversing EBV-mediated immune evasion. Targeting ferroptosis regulators (SLC7A11, GPX4, FTO, CD38) overcomes resistance, positioning ferroptosis modulation as a transformative strategy for NPC management.

Leveraging the overexpression of cluster of differentiation 36 (CD36) in breast cancer cells, DCP-TPP employs fatty acid camouflage (PCM) to deliver disulfiram (DSF) and photothermal Cu3BiS3 to cancer cells and features triphenylphosphonium (TPP) modification for targeted mitochondrial drug delivery...In breast cancer models, DCP-TPP achieved 90.9% tumor suppression, with 60% of mice resisting rechallenge. By transforming lipid metabolic dependency into a therapeutic vulnerability and coupling it with copper ion toxicity, DCP-TPP offers a promising strategy for breast cancer therapy.

P1, N=60, Recruiting, Columbia University | Not yet recruiting --> Recruiting

Additionally, the natural alkaloid trigonelline has shown promise in reversing Nrf2-mediated ferroptosis resistance in cisplatin-refractory tumors. Pharmacologic agents such as auranofin, fucoxanthin, carnosic acid, and disulfiram/copper complexes have demonstrated efficacy in sensitizing HNC to ferroptosis by disrupting the Nrf2 axis. This review summarizes emerging mechanisms of ferroptosis evasion and highlights therapeutic strategies targeting the Nrf2-ferroptosis network. Integrating ferroptosis inducers with immune and chemotherapeutic approaches may provide new opportunities for overcoming resistance in head and neck malignancies.