P=N/A, N=40, Not yet recruiting, the First Affiliated Hospital, Zhejiang University School of Medicine; The People's Hospital Affiliated to Ningbo University

SRSF2 mutations promoted DNR resistance through multiple mechanisms, and targeted combination therapy with PDGFB pathway inhibitors may represent a novel strategy to improve therapeutic outcomes in patients with mutations.

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.

Although arsenic trioxide (ATO) can restore transcriptional activity of structural p53 mutants, its clinical application is limited by subtype selectivity and systemic toxicity...Upon tumor-specific release, allicin-mediated redox activation converts As5+ to cytotoxic As3+, enabling selective p53 reactivation, concurrent ATR inhibition, and H2S-amplified apoptosis. AsAcP@LP exhibits synergistic antitumor efficacy with favorable tolerability, providing a rational nanotherapeutic strategy for p53-mutant cancers.

(3) Clinical evidence confirms that ATRA combined with arsenic trioxide or epigenetic modulators achieves high remission rates in APL and selected AML subtypes...(4) ATRA-based combination therapies represent a promising strategy to extend differentiation therapy beyond APL. This review, authored solely by the investigator, highlights molecular targets and potential enhancers warranting further clinical evaluation in AML.

Next, two gastric cancer cell lines (AGS, HGC27) were selected for in vitro experiments to assess the combined effects of PUN and the copper ionophore elesclomol (ES) (hereafter referred to as ES-Cu, representing the combination of ES and Cu2+)...In combination therapy strategies, PUN can work synergistically with chemotherapy drugs to suppress gastric cancer growth. Furthermore, PUN enhances its inhibitory effect on gastric cancer by working synergistically with cuproptosis through targeting FDX1.

The mechanisms involve suppressing ROS generation, maintaining mitochondrial membrane stability, enhancing cell viability, migration, and proliferation, as well as inhibiting Jnk and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways. The findings highlight potential molecular targets and novel strategies for the clinical prevention and treatment of ATO-related toxicity .

ISL1 serves as both a predictive biomarker and functional dependency, as evidenced by essentiality for cell survival and loss following treatment. Prospective studies using ISL1 as a predictive biomarker for lurbinectedin are planned.

KLF4 serves as a hub gate orchestrating cell crosstalk within the TME. Understanding its context-dependent functions may facilitate the development of KLF4-targeted therapies for precision oncology.

SLC7A11 knockdown regulates intracellular redox balance through the GSH-GPX4 axis, thereby promoting cellular cuproptosis. Targeting SLC7A11 can enhance the sensitivity of CRC cells to copper ionophores and may represent a novel therapeutic strategy to enhance cuproptosis of CRC cells.

In contrast, co-treatment with Cu and copper ionophore elesclomol (Cu-ES) triggered cuproptosis, a unique copper-dependent form of cell death, accompanied by mitochondrial dysfunction, dihydrolipoamide S-acetyltransferase aggregation, and ATP depletion. The PLK1 inhibitor BI-2536 recapitulated the effects of Cu-ES and exhibited synergistic activity when combined with Cu-ES, enhancing both cell death and EMT suppression. These findings highlight a novel regulatory mechanism of EMT through copper signaling and support copper-based combination therapies as a promising approach to simultaneously inhibit tumor growth and metastasis in colorectal cancer.

This inhibition collectively diminishes the expression and activity changes in complex IV, induces mitochondrial dysfunction, and promotes cuproptosis in ovarian cancer. This study further demonstrates that inhibiting the oxidative phosphorylation complex IV can enhance copper-induced cell death in ovarian cancer.