elesclomol (STA-4783)

CCNJL has the potential to act as a valuable prognostic indicator and immunotherapy target in CHOL. Its expression pattern and associations with clinical outcomes, immune characteristics, and drug sensitivity highlight its potential for improving diagnostic and therapeutic approaches. Future research should focus on elucidating the underlying mechanisms and validating these findings in larger cohorts.

The combination of elesclomol (a cuproptosis inducer) and selisistat (a SIRT1 inhibitor) effectively induced cuproptosis in CRC. Moreover, DLAT supplementation establishes a positive feedback loop that amplifies cuproptosis. These results underscore the critical role of nonhistone NAT10 lactylation in tumor cuproptosis and highlight the therapeutic potential of targeting this pathway for CRC treatment.

This resulted in intracellular Cu+ accumulation, triggering cuproptosis and excessive mitophagy, ultimately suppressing tumor growth. Therapeutically, the copper ionophore elesclomol potently inhibited tumor growth in a Thumpd1-knockout mouse model of LUAD.

Addressing this limitation, combination therapies integrating elesclomol with targeted agents such as ferroptosis inducers or chemotherapeutic drugs have demonstrated significant antitumor advantages. Future research must urgently leverage the selection of precise biomarkers and the development of novel intelligent nanodelivery systems to further advance the safe and efficient clinical translation of elesclomol.

CuCl2 and elesclomol treatment induced cuproptosis, which was attenuated by SLC39A4 overexpression but potentiated by SLC39A4 knockdown, as confirmed through proliferation assays and cuproptosis marker analyses in cell cultures and xenograft models...Dual-luciferase assays demonstrated that mutation of the m6A site within SLC39A4's coding sequence abolished YTHDF1-mediated regulation. These findings establish SLC39A4 as a promoter of GC progression through cuproptosis suppression, modulated by YTHDF1 via m6A-dependent mRNA stabilization, revealing potential therapeutic targets for GC treatment.

USP15 depletion or elesclomol (ES)-Cu/disulfiram (DSF)-Cu restored sunitinib sensitivity both in vitro and vivo without systemic toxicity. Collectively, our findings identify USP15 as a critical regulator of cuproptosis and sunitinib resistance and highligh cuproptosis activation as a promising strategy to overcome tyrosine kinase inhibitor (TKI) resistance in ccRCC.

Multi-omics-guided drug screening revealed that Cluster 3 displays particular sensitivity to both Elesclomol and the clinically available proteasome inhibitor Bortezomib. Of particular translational relevance, the Venetoclax-Bortezomib combination leverages an agent with an established safety profile, offering a readily implementable strategy for near-future clinical translation. Our study establishes a novel multi-omics classification system that provides a robust foundation for investigating biological heterogeneity, elucidating resistance mechanisms, and developing effective combination strategies to achieve personalized therapy in AML.

We depict NeuLysis (NEU1-induced Lysosomal Escape leading to mitochondrial Lysis) as a novel cell death pathway in glioblastoma, wherein PTRF-NEU1 axis prolonged mitochondria-lysosome contacts. Pharmacological NEU1 inhibition with Oseltamivir synergizes Elesclomol-induced cell death, providing a preclinically actionable therapeutic strategy against glioblastoma.

In this study, we demonstrate that IDH1-mutant AML cells are markedly more sensitive to cuproptosis induced by the copper ionophore elesclomol (ES), compared to their wild-type counterparts...In vivo experiments confirm that ES more effectively suppresses tumor growth in IDH1-mutant xenografts. These findings uncover a copper-dependent metabolic vulnerability and provide a rationale for exploiting cuproptosis as a therapeutic strategy in IDH1-mutant AML.

This study highlights FINs as effective cuproptosis potentiators and suggests a novel combinatorial regimen that simultaneously targets cuproptosis and ferroptosis, offering dual antitumor and bone-protective benefits for OS therapy.

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.

Consequently, cells switch from the tricarboxylic acid (TCA) cycle respiration to glycolysis, reducing sensitivity to the copper ionophore elesclomol (ES)...HBx-mediated repression of SIRT3 disrupts STEAP4 deacetylation and mitochondrial targeting, fostering metabolic reprogramming and evasion of copper-induced cell death. The results provide a pre-clinical rationale for copper-directed combination strategies in HBV-associated HCC.