P1/2, N=32, Recruiting, West China Hospital of Sichuan University; West China Hospital of Sichuan University

In this study, elesclomol (ES) or disulfiram (DSF)/Cu was used to induce cuproptosis, and bathocuproine disulfonic acid (BCS) was used to inhibit it. In vivo, the role of the ALKBH5-ATOX1 axis in AML progression has also been confirmed. In Conclusion, The demethylase ALKBH5 downregulates ATOX1 by reducing its m⁶A levels, thereby modulating cuproptosis in AML-a mechanism that offers potential novel insights and therapeutic targets for AML treatment.

In addition, DSF/Cu combined with IR treatment inhibited tumor growth and enhanced tumor-infiltrating immune cells in the B16F10-bearing C57BL/6 model. Our findings reveal that combining IR with DSF/Cu induces ICD and inhibits tumor growth in melanoma, providing a promising strategy to overcome the inherent resistance of RT in melanoma.

Moreover, high levels of expression of TRMT10C and PCSK9 in human HCC tumor tissues were associated with poor prognosis, while c-FOS showed the opposite pattern, confirming that the TRMT10C-c-FOS-PCSK9 axis is an important mechanism in HCC. In conclusion, copper ion carrier-DSF promotes the expression of c-FOS by inhibiting the m1A methyltransferase TRMT10C, thereby reversing the dysregulation of lipid metabolism and inhibiting angiogenesis in HCC.

These include next-generation tyrosine kinase inhibitors (TKIs), KRAS12C inhibitors, bispecific antibodies including ivonescimab, and they all are specific to inhibit predominant signalling cascades that promote tumoral proliferation and resistance...Pharmacological modulators of autophagy including statins, disulfiram, and lysosomotropic agents (e.g., chloroquine) target metabolic vulnerabilities such as mitochondrial bioenergetics and redox homeostasis...Also, inhalable nano formulations and targeted drug-delivery systems optimize the bioavailability of the formulation by pulmonary determination and ameliorates the systemic toxicity. A combination of these therapeutic approaches will provide a more accurate and flexible way of conquering MDR in lung cancer.

In vivo studies using a mouse tumor model supported these findings, demonstrating significantly inhibited tumor growth in the DSF/Cu group compared with the control group. Overall, our study findings suggest that the DSF/Cu combination exhibits significant therapeutic potential against HCC by modulating the ATF3-dependent mitochondrial apoptosis pathway, a strategy that warrants further preclinical exploration.

Disulfiram and eugenol were predicted as potential therapeutics and validated by docking...This study identifies mitochondrial gene signatures associated with BC and proposes a computational model distinguishing tumor from normal tissue. These findings offer potential leads for future biomarker development but require additional clinical and functional validation.

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.