elesclomol (STA-4783)

The effects of the SNHG26-CDKN2A axis on Cu + ELES(copper plus elesclomol)-induced cuproptosis and CD8+ T cell-mediated anti-tumour immunity were evaluated through cell viability, apoptosis, co-culture cytotoxicity and migration assays...Our findings reveal a novel regulatory axis whereby SNHG26 promotes CRC progression by destabilising CDKN2A mRNA, resulting in enhanced cell proliferation, cuproptosis and immune evasion. This study provides new insights into the molecular mechanisms underlying CRC development.

In vivo experiments revealed that ES inhibited tumor growth and upregulated PCK2. Taking together, our findings reveal that the ES-ER stress-PCK2 axis is a critical mediator of copper-induced metabolic disruption, providing a rationale for targeting cuproptosis pathways in LUAD therapy.

In vitro experiments, the combination of elesclomol (a copper ion carrier) and bortezomib (Bortezomib) demonstrated a synergistic anti-myeloma effect through excessive intracellular reactive oxygen species generation. This study provides valuable insights into the role of CRGs in MM, potentially aiding in prognosis prediction and the development of effective, personalized therapeutic strategies.

The 15q15 deletion promotes BM development through aberrant MYC signaling and the subsequent reprogramming of carbohydrate metabolism.

Furthermore, our results demonstrated that the combination of Elesclomol with HSP90 inhibitor Ganetespib exhibited synergistic anti-tumor effects. In conclusion, our findings that mitochondria-translocated ALDH1L1 functions as a feedback regulator of redox homeostasis in cancer cells to enhance the resistance to pro-oxidative therapy can provide critical insights into developing effective pro-oxidative therapies against tumors.

Finally, overexpression of CRT and NLRP3 activates the DCs-CD8+ T cell immune response axis through the lymphocyte-mediated immunity pathway, enabling effective immunotherapy. Considering the in vivo pH-responsive biodegradability in the tumor immune microenvironment (TIME), our study has provided an impetus for the design and preparation of copper-based nanomaterials, which are efficacious in OS immunotherapy.

Here, we fabricated a PD-L1 nanobody-engineered bacterial outer membrane vesicles (OMVs) delivering elesclomol (ES) micelles for enhanced immunotherapy in triple-negative breast cancer (TNBC)...Notably, our nanoparticles elicited a robust antitumor immune response with increased infiltration and activation of CD8+ T cells and Treg depletion. By integrating cuproptotic tumor death with immune checkpoint blockade, the dual-functional nanoplatform represents a promising strategy for potentiated immunotherapy.

Two major strategies were pursued: (i) inhibiting copper transporters ATP7A and B with tranilast (TR) and omeprazole (OM) to block the cellular copper and, potentially, also cisplatin efflux, and (ii) using the chelator elesclomol (ES) to elevate intracellular copper and cisplatin levels. Moreover, all drugs contributed to the enhanced cellular anticancer activity of cisplatin, with ES being the most effective compound. The results suggest that the targeted modulation of copper transport mechanisms may offer novel adjuvant approaches for the treatment of PDAC.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis, partly due to cancer stem cells (CSCs) that drive progression and treatment resistance. In vivo, in aggressive immunocompetent murine PDAC models, this nanoparticle-based treatment significantly improved gemcitabine response. These findings identify nanoparticle-mediated cuproptosis induction, combined with standard chemotherapy, as an innovative CSC-targeting strategy to improve PDAC outcomes, offering new hope for PDAC patients.

A549 cells were treated with elesclomol (ES-Cu) and tetrathiomolybdate (TTM) to induce or inhibit cellular cuproptosis...Finally, we verified that RBM15 promoted tumor growth by mediating SRSF1 in vivo. In short, RBM15-mediated m6A modification enhanced SRSF1 stability, and SRSF1 promoted ATP7B alternative splicing to inhibit cuproptosis, thereby promoting NSCLC cell proliferation and tumor growth.

This study deepens the understanding of GBM by pinpointing critical genetic markers and elucidating their influence on the tumor immune microenvironment (TME) as well as treatment response. The risk model developed in this study holds promise for enhancing prognostic accuracy and facilitating the personalization of GBM therapy.

The copper chelator tetrathiomolybdate weakens the inhibiting effect of Tan IIA on cell viability; while Tan IIA enhances the inhibiting effect of elesclomol-Cu on cell viability...The effectiveness of SAH in Tan IIA promoting cuproptosis and antitumor utility is demonstrated in a xenograft tumor model. Tan IIA exerts an anti-bladder cancer effect by promoting the cuproptosis of tumor cells, and the possible mechanism is to promote the expression of FDX1 by METTL3/METTL14-mediated the increasing FDX1 m6A modification.