P1, N=24, Recruiting, Case Comprehensive Cancer Center | Trial primary completion date: Apr 2026 --> Sep 2026

For the cuproptosis, Rh1 promoted the elesclomol-Cu (ES-Cu) or disulfiram-Cu induced proliferation inhibition. Finally, this work verified that Ginsenoside Rh1 promoted the cuproptosis and repressed the immune evasion of GC cells. In short, Ginsenoside Rh1 attenuated the ATP7A to potentiate the copper accumulation and cuproptosis, thereby alleviating cuproptosis-related immune evasion.

We developed a game-theoretic mathematical model, parameterized from this in vitro experimental data, and used it to predict the existence of a double-bind, where selection for resistance to chemotherapy induces sensitivity to disulfiram. The model predicts a dose-dependent re-sensitization to chemotherapy for monotherapy disulfiram.

Keyword and co-citation analyses revealed a thematic shift from foundational mechanistic studies toward prognostic modeling, copper ionophore exploration (e.g., elesclomol and disulfiram), immune-related analyses, and bioinformatics-driven patient stratification. The strong geographic concentration of publications and limited international collaboration highlight structural imbalances in knowledge production and the need for broader global validation. This bibliometric mapping clarifies the field's early developmental stage and identifies priorities for future research, including cross-regional collaboration, experimental standardization, and cautious advancement toward clinical application.

Animal studies have indicated that disulfiram/copper (DSF/Cu) can target the NPLOC4 protein, and that the combination of DSF/Cu with PD-1 therapy significantly inhibits HCC growth. In conclusion, targeting NPLOC4+ TAMs can significantly increase the resistance of HCC to anti-PD-1 therapy, which makes it a promising novel immune target for HCC treatment.

Pharmacological inhibition of pyroptosis with disulfiram (DSF) significantly alleviates WMI in vitro and in vivo. These findings highlight microglia pyroptosis as a potential therapeutic target to prevent neurodevelopmental impairment in the developing brain following hypothermic hypoxia-ischemia.

This study demonstrates that CuET exhibits markedly enhanced anti-tumor activity against Ewing sarcoma compared with its precursor compounds, DDTC and copper ions. Furthermore, we identify ESM1 as a potential regulatory factor that dually governs sarcoma proliferation and confers resistance to CuET, primarily through activation of the MAPK/ERK signaling cascade. Significantly, targeting the ESM1-MAPK/ERK axis synergistically enhances the therapeutic efficacy of CuET treatment. In summary, this research establishes a foundation for future investigations and novel therapeutic strategies in the field of Ewing's sarcoma of bone.

This concept is exemplified by compounds (1) and (2), in which bulky substituents confer selective inhibition of ALDH1A1 while sparing ALDH2. This review provides a comprehensive overview of DSF analogs, their molecular mechanisms, and therapeutic potential, highlighting their promise as multifunctional agents for cancer, metabolic disorders, infectious diseases, and radioprotection.

According to our results, TMZ-DSF-Cu significantly increased mean survival and induced both LC3 and p62 autophagy markers. Interestingly, these results could not be achieved in the absence of Cu, neither in the presence of TMZ alone, suggesting the importance of combining DSF with Cu in order to sensitize glioma to TMZ, presumably via implication of autophagy modulation.

Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting IL-1β in KRAS-mutant BTC...These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.

Furthermore, E171-induced secretion of S100A8 and S100A9 in macrophages was suppressed by specific inhibitors, including N-acetylcysteine (NAC, ROS inhibitor), MCC950 (NLRP3 inhibitor), Z-YVAD-FMK (caspase 1 inhibitor), disulfiram (GSDMD inhibitor), and transfection of NLRP3 small interfering ribonucleic acid (siRNA). These results indicate that dietary E171 promotes CAC development by activating macrophages, with S100A8 and S100A9 serving as key mediators, and the NLRP3/caspase 1/GSDMD pathway acting as a critical mechanism.

Fifty-six mice were randomly allocated into four groups, including control, diabetic constipation (DC), disulfiram, and propargylglycine (PAG)...The results of this study demonstrated that H2S is an effective and key factor in regulating colonic motility in mice with DC. In the future, inhibitors of H2S production may be used to manage the digestive complications associated with DC.