The significantly differentially expressed genes (DEGs) from the Gene Expression Omnibus (GEO) database, which discriminate AGS and MKN45 cells in the presence of DMSO and verteporfin (a chemotherapy reagent), are determined...MKN45 was highlighted as more invasive cancer cell relative to AGS cells. PLOD2 was pointed out as a suitable target in the chemotherapy of gastric cancer.

This study identified a novel CAF-exosome-YAP-USP8-HER2 signaling axis that drives trastuzumab insensitivity in HER2-positive breast cancer. Intervening in this pathway may represent a potential treatment approach to counteract microenvironment-induced chemoresistance.

P1/2, N=19, Completed, Roswell Park Cancer Institute | Terminated --> Completed

P1/2, N=12, Not yet recruiting, Odense University Hospital

In an immune-cold syngeneic mouse PDAC model, 690 nm light activation of SM-102-containing liposomes slowed tumor growth by up to 56% and extended survival by 40%. Together, these findings suggest that integrating SM-102 into light-activated liposomes is a simple and robust strategy to enhance photochemical ICD and may improve therapeutic outcomes in immunotherapy-based combinations that utilize liposomal drug delivery systems.

We summarize opportunities and unresolved challenges in leveraging copper ionophores (e.g., elesclomol and disulfiram) and high-affinity chelators (e.g., tetrathiomolybdate) across malignant and non-neoplastic diseases. Furthermore, we address the translational challenges of precision delivery, including the use of nanoparticle-based systems to enhance therapeutic indices and the identification of biomarkers for patient stratification. By integrating recent pre-clinical and early clinical data (2023-2025), we suggest that targeting the mitochondrial-copper axis represents a promising, yet still experimentally grounded, avenue in precision medicine, while emphasizing current limitations in biomarker validation, delivery selectivity, and safety profiling.

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.

P1/2, N=66, Recruiting, SpectraCure AB | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Jul 2027

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.