XBP1s negatively regulates the protein level of LIPT1 to inhibit LUAD cell death induced by copper-loaded ionophore elesclomol...Co-administration with SEs inhibitor and copper ionophore also markedly reduced tumor volume and growth rate. Our study sheds light on the molecular mechanism by which XBP1s affect the cuproptosis through super-enhancers formation in LUAD and suggested the potential clinical value of copper ionophore as well as a potential biomarker XBP1s for treatment response.

P2, N=92, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Therapies that enable cells to circumvent the differentiation block, such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), are by and large curative in acute promyelocytic leukaemia3, but whether 'differentiation therapy' is a generalizable therapeutic approach for acute myeloid leukaemia (AML) and beyond remains incompletely understood...Analysis of datasets from patients with AML suggests a correlation between the combination-induced transcription signature and better prognosis, highlighting clinical potential of this strategy. Collectively, this combination strategy rewires transcriptional programs to suppress stemness and to promote differentiation, which may have important therapeutic implications for AML and WNT-driven cancers beyond AML.

Together, our findings are the first to identify the central role of FDX1 in synergizing with ES to activate IFN-β signaling and induce PANoptosis. This study enables us to re-explore the clinical anticancer potential of ES as a novel therapeutic strategy for DLBCL.

Acute myeloid leukemia (AML) is characterized by the clonal expansion of myeloid progenitors blocked at various stages of their differentiation process, and drugs that bypass this differentiation block are therapeutically efficient, as shown by retinoic acid and arsenic trioxide in acute promyelocytic leukemia...However, the development of molecular studies has led to the identification of therapeutic targets (such as mutated proteins and deregulated pathways) and has led to the generation of a new category of specific pharmacologic agents. Some of these agents, such as inhibitors of mutant isocitrate dehydrogenase (IDH1 and IDH2), lysine-specific demethylase-1 (LSD1), and Menin, have shown the capacity to induce leukemic cell differentiation and with significant therapeutic efficacy.

This study aimed to investigate the radiosensitizing effects of arsenic trioxide (ATO) on CC and explore its underlying molecular mechanisms...These findings provide theoretical and experimental support for using ATO as a radiosensitizer in CC therapy, potentially leading to improved treatment outcomes, reduced recurrence rates, and enhanced patient survival. Future research should focus on optimizing ATO's dosage and timing as well as evaluating its long-term safety and efficacy in clinical settings.

The characteristics of the transcriptome in peripheral blood and single-cell transcriptome in the prefrontal cortex exhibit significant differences between male and female patients with AD, which providing a basis for future sex stratified treatment of AD.

Consequently, we purified the RING, B-box1, and B-box2 domains to assess their potential for arsenic-binding. The results showed that ATO cannot displace zinc ions under physiological conditions but binds with zinc finger domains under zinc-depletion in low-pH conditions, revealing a conditional binding mechanism.

Herein, elesclomol (ES) and glucose oxidase (GOx) co-loaded CuFe2O4 (CF) nanoplatform (termed as CFEG) was elaborately engineered to boost cuproptosis through multi-pathway copper metabolisms regulation...Collectively, such the multi-pathway copper metabolisms regulation including improved Cu influx, inhibited Cu efflux and GSH depletion significantly boosted cuproptosis, which synergized with photothermal effect of CF to efficiently repressed the growth of tumor in mice without causing systemic toxicity. This work provides a multivariate mode for enhanced tumor cuproptosis therapy, and may also inspire the design of advanced cuproptosis-related nanomedicine system.

As a result, low-dose arsenic trioxide induces ER-stress and inhibits proliferation in cultured cell lines and animal models. Our work identifies a strategy to treat cancers with APC deletion and provides a framework for identifying and translating vulnerabilities associated with loss of a TSG.

First-line induction treatment includes the combination of all-transretinoic acid (ATRA) and arsenic trioxide, with which complete response rates greater than 90% are achieved...We report the case of a woman with APL who, during the induction phase of treatment, presented myositis of the pelvic muscles and lower extremities secondary to the administration of ATRA. The condition resolved after the administration of corticosteroids and temporary suspension of ATRA, with no recurrence after its restart.

P=N/A, N=272, Active, not recruiting, Jazz Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Jun 2030 --> Jun 2025 | Trial primary completion date: Jun 2030 --> Jun 2025

Arsenic trioxide (ATO), carboplatin (CP), and cyclophosphamide (CY) are used to treat various cancers. The combination of ATO, CP, and CY induces synergistic effects in promoting apoptosis and autophagy in TNBC cell lines. These findings suggest that this combination therapy could be a promising approach to enhancing treatment efficacy in aggressive breast cancers, offering new insights into potential therapeutic strategies.

P2, N=25, Active, not recruiting, Mridula George, MD | Recruiting --> Active, not recruiting | Trial completion date: Sep 2024 --> Jun 2025 | Trial primary completion date: Jun 2024 --> Jun 2025

P2/3, N=610, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College.; Institute of Hematolog

P1/2, N=0, Withdrawn, Vall d'Hebron Institute of Oncology | N=15 --> 0 | Not yet recruiting --> Withdrawn

This effect is achieved by reducing the CD11b+CD45dim microglia population and iNOS expression, restoring the expression of protein-95 (PSD-95) and synaptophysin. These findings indicated that PANE represents an efficient platform for delivering circRNAs to the brain, and intranasal administration of PANE2-4-circDYM is a promising strategy for ameliorating LPS-induced depressive-like behaviors.

A strong additive association between CYP3A4 and CYP3A5 genotypes (informed as a CYP3A activity score [AS] variable) and lurbinectedin clearance (CL) and exposure was confirmed, for example, patients with an AS of 3, 2, or 1 showed a 2.3-, 1.6-, and 1.5-fold higher total lurbinectedin CL compared to those with an AS of 0 and 2.3-, 1.8-, and 1.6-fold higher unbound lurbinectedin CL. In conclusion, preemptive CYP3A genotyping may offer a valuable approach for personalizing treatment with lurbinectedin in cancer patients.

Arsenic trioxide (ATO) targeting MCM7 could inhibit the CSC phenotypes and enhance the efficacy of radiotherapy in vivo and in vitro. Collectively, histone lactylation could transcriptionally activate MCM7 to accelerate proliferation and radio-resistance through enhancing CSC properties. ATO targeting MCM7 could inhibit CSCs phenotypes and synergistically increase the efficacy of radiation therapy.

The anti-tumor effect of ATF3 inducer 1-targeted upregulation of PER2 combined with copper ionophore elesclomol (ES) was found to be significantly enhanced compared with that of monotherapy in an OSCC xenograft model. These findings reveal a critical role of ATF3-dependent regulation of cuproptosis by PER2 in OSCC development, suggesting targeted upregulation of PER2 or ATF3 in combination to induce cuproptosis as a novel strategy to potentially improve the prognosis of OSCC patients.

Furthermore, anti-programmed cell death protein 1 immunotherapy strongly downregulated the expression of APOC1 in patients with ACC. Both pilaralisib and elesclomol strongly inhibited SW13 cell growth.ConclusionsThis study preliminarily clarified that APOC1 and APOE might be potential therapeutic and prognostic targets for ACC, and identified new targets and treatment strategies for ACC.

The authors present a case in which IN cancer therapy with NEO100 was well tolerated and was associated with striking tumor regression, providing further evidence that this novel conceptual approach to cancer therapy might become useful for the improved treatment of recurrent glioma. https://thejns.org/doi/10.3171/CASE24683.

The introduction of immune checkpoint inhibitors, such as atezolizumab and durvalumab, in combination with traditional chemotherapy, has marked a significant advancement, demonstrating improved overall survival and progression-free survival compared to chemotherapy alone...New treatment modalities, such as lurbinectedin and anti-Delta-like Canonical Notch Ligand 3 antibodies, are now included in the treatment options for refractory SCLC, and many more treatment strategies involving combination therapies are being studied. Advances in molecular profiling and the identification of biomarkers are aiding in the development of personalized treatment approaches. This review focuses on these recent advancements and emerging strategies in the treatment of ES-SCLC.

Elesclomol (ES) is a Cu2+ transporter that delivers Cu2+ into tumor cells, causing cell death at toxic doses...Additionally, the combined anti-tumor efficacy of TSF@ES-Cu and αPDL-1 is 1.6 times higher than TSF@ES-Cu alone and 2.5 times higher than αPDL-1 alone. In summary, this study reports that the combination of TSF@ES-Cu and αPDL-1 effectively induces cuproptosis and reshapes the TME, offering a new approach for copper nanomaterial-based tumor immunotherapy.

Combination therapies with ginger extract, gold nanoparticles, and arsenic trioxide (ATO) have been investigated to augment MTX's cytotoxic effects. This review delineates MTX's therapeutic roles, elucidates its resistance mechanisms, and discusses current and potential strategies for managing MTX resistance to bolster treatment effectiveness in pediatric tumors and other diseases. This knowledge base could underpin further research and development of personalized treatments to optimize MTX's clinical benefits.

This study indicates that FOXP3 plays an oncogenic role in breast cancer development and suggests that targeting IGF1R-FOXP3-β-catenin signaling may be a putative therapeutic strategy for human breast cancer treatment.

Arsenic trioxide (ATO) is an effective therapeutic agent for acute promyelocytic leukemia; however, its long-term use can lead to cardiotoxicity, particularly in cases of acquired long QT syndrome (acLQTS), which may result in torsade de pointes (TdP)...Tanshinone IIA and fexofenadine restored the hERG protein levels potentially by decreasing MALAT1 expression and counteracting ATO's effects on the MALAT1/calpain-1 pathway. Collectively, our research uncovers a previously unreported regulatory mechanism underlying ATO-induced acLQTS. Moreover, it identifies potential molecular targets and intervention strategies for acLQTS therapy.

The sensitivity of three common drugs (homoharringtonine, lapatinib, and palbociclib) in LUAD could be evaluated by the CR-relevant risk model. Ultimately, the experimental results confirmed that the expression trends of CDK1 and HLA-DMA in our collected clinical samples were in line with the expression trends in the TCGA-LUAD dataset. In conclusion, a CR-relevant risk model based on CDK1 and HLA-DMA was constructed by using bioinformatics analysis, which might supply a new insight into the improved prognosis of LUAD.

P2/3, N=610, Not yet recruiting, Institute of Hematology & Blood Diseases Hospital, China

P2, N=47, Terminated, Jazz Pharmaceuticals | Completed --> Terminated; Termination of this study was a business decision made during portfolio review.

Our study suggests candidate molecular mechanisms linking periodontitis to prostate cancer, highlighting potential compounds targeting both diseases. These findings provide a foundation for guiding future basic and clinical research.

P3, N=135, Completed, Technische Universität Dresden | Active, not recruiting --> Completed | N=280 --> 135

In the p53 R279W (equivalent to the human hotspot R282W) mouse model developing spontaneous tumors, arsenic trioxide (ATO) treatment through drinking water significantly prolongs the survival of mice, dependent on p53-R279W reactivation...ATO also activates the IFN pathway in human cancer cells harboring various p53 mutations, as well as in primary samples derived from the p53-mutant patient treated with ATO. Together, p53 could serve as an alternative therapeutic target for the development of immunotherapies.

Through fluorescence tracing of the SsCtr3 transporter and copper ions combined with elesclomol induction, we found that the ESCRT pathway mediates SsCtr3 to sequester excess copper into vacuoles under high‑copper stress...Pathogenicity assays revealed that disrupting the ESCRT pathway significantly enhances efficacy of copper-based compounds treatments. By elucidating the molecular crosstalk between fungal copper transport and cuproptosis suppression, this study delineates the fungus's copper homeostasis-cuproptosis axis, providing a strategic framework for optimizing copper-based disease control in sugarcane and related crops.

P1, N=30, Recruiting, Virginia Commonwealth University | Not yet recruiting --> Recruiting

MLKL inactivation reduces such autophagy and renders the cells sensitive to autophagy inhibitors, such as homoharringtonine. Hence, MLKL inhibition creates a therapeutic vulnerability that could be utilized for CRC treatment.

P1/2, N=5, Terminated, Genprex, Inc. | N=180 --> 5 | Trial completion date: Dec 2025 --> Feb 2025 | Active, not recruiting --> Terminated; Enrollment was slow, due to competition with the many other clinical trials for the same patient population, which led to the decision to end enrollment in the trial.

The contents of copper, malondialdehyde (MDA), pyruvic acid and mitoSOX as well as the ratio of cells with low mitochondrial potential increased significantly in the hemocytes upon elesclomol treatment and the content of citric acid decreased significantly. These findings suggest the potential presence of cuproptosis in oysters and its activation mechanism is relatively conserved in evolution.

Moreover, aprocitentan administration strikingly reversed DOX-induced and elesclomol-aggravated cellular senescence and mitochondrial injury in cardiomyocytes. More importantly, knock-down of sirtuin 7 (SIRT7) by SIRT7 siRNA blocked the beneficial effects of aprocitentan on DOX-associated cuproptosis, oxidative stress, mitochondrial injury, and senescence in cardiomyocytes. In summary, aprocitentan exerts as a novel therapeutic agent for alleviation of DOX-induced cardiotoxicity through the inhibition of cuproptosis, oxidative stress, cardiac aging and mitochondrial injuries via the activation of SIRT7, offering new possibilities for prevention and treatment of DOX-induced cardiac disorders.

We present an uncommon case of a humeral APL/GS, and conducted a comprehensive analysis of 28 cases of APL/GS. Despite the rarity of APL/GS, it should be diagnosed at an early stage. Furthermore, ATRA are recommended in the treatment plan of APL/GS.

This study demonstrates that TWIST1 regulates the ubiquitination and degradation of HK2, thereby promoting glycolysis-induced cuproptosis and facilitating pancreatic cancer invasion and metastasis. Understanding the underlying mechanisms of PDAC, including the regulation of key proteins such as HK2 by TWIST1, is crucial for developing more effective treatment strategies. Findings highlight the importance of targeting these molecular pathways, which could lead to improved diagnostic and therapeutic approaches, ultimately enhancing patient outcomes and prognosis.

P3, N=876, Recruiting, Nanfang Hospital, Southern Medical University