Furthermore, IFN-γ facilitates erastin- and RSL-3-induced ferroptosis of tumor cells, particularly in temozolomide (TMZ)-resistant cells. Additionally, OMV-C-C@RSL-3 synergistically suppresses GBM growth in vivo. Thus, biosynthetically engineered OMV-C-C integrates intrinsic immunomodulatory activity with ferroptosis enhancement to strengthen glioblastoma immunotherapies, offering a versatile platform to overcome limitations in brain tumor immunotherapy.

Mechanistically, SPI1 transcriptionally suppresses ACSL4 expression through the EZH2/H3K27me3 pathway, leading to inhibition of intracellular lipid peroxidation. Thus, SPI1 knockdown synergizes with erastin to promote lipid peroxidation and ferroptosis, suggesting that targeting SPI1 may represent a promising therapeutic strategy for renal cell carcinoma.

Furthermore, RNPS1 overexpression attenuated erastin-triggered ferroptosis by suppressing the accumulation of lipid ROS and malondialdehyde, as well as by preventing the depletion of glutathione...Importantly, blocking ETV4 expression partially reversed RNPS1 overexpression-mediated suppression of ferroptosis. Collectively, these results support the notion that RNPS1 acts as a novel suppressor of ferroptosis in NSCLC progression.

Importantly, combining GTN with the ferroptosis inducer RSL3 synergistically enhances antitumor efficacy in vivo. Our study unveils a previously unrecognized KDM5B/ferroptosis axis through which GTN exerts its antitumor effects, positioning GTN as a promising lead compound for ferroptosis-targeted therapy in RCC.

The rescue experiments (overexpression of BCL11A combined with IFI6 or ferroptosis activator Erastin) were conducted to clarify the mechanism. Co-overexpression of IFI6 rescued the phenotype. This study reveals that BCL11A promotes ferroptosis by transcriptional inhibition of IFI6, thereby reducing TMZ resistance in glioma cells, providing a new strategy for combined targeting of IFI6 and ferroptosis.

In mouse models of melanoma and colorectal cancer, I3A administration significantly reduced the antitumor efficacy of the ferroptosis inducer RSL3, accompanied by reduced lipid peroxidation and preserved GPX4 levels. Furthermore, gut colonization with Lactobacillus reuteri increased I3A concentration and conferred ferroptosis resistance in vivo. Together, these findings identify a host-microbe metabolic axis in which microbial I3A suppresses cancer cell ferroptosis through AHR-JNK signaling, which may have critical implications for redox-based cancer therapies.

Firstly, the dual pathway specific enrichment strategy of O-GlcNAc modified peptides and N-glycosylated peptides was applied to ferroptosis study for the first time, which realized a systematic analysis of glycosylation patterns in the process of cell death. Secondly, high-resolution mass spectrometry combined with multi-platform data processing (MaxQuant/PEAKS) was used to deeply integrate transcriptomes and single-cell transcriptomes to construct a panoramic analysis framework with multi-omics mutual evidence. Thirdly, Scissor method was introduced to map TCGA ferroptosis pathway activity to single-cell data to achieve cross-scale analysis from population level to cell subsets. Fourth, combined with multi-dimensional bioinformatics tools, the characteristics of modification sites, subcellular localization, protein interaction network and functional pathway were annotated. Fifth, on the basis of multi-omics results, double-layer validation by qPCR and Western Blot at the transcriptional and protein levels significantly improved the credibility of the research conclusions. Its limitations are that the research mainly relies on high-throughput omics and computational analysis, and lacks systematic in vitro and in vivo functional verification and combination drug sensitivity experiments, as well as the support of real-world clinical cohorts.

Ferroptosis was induced in B-ALL cells using erastin...PRDX1 knockdown further reduced the viability of B-ALL cells treated with the ferroptosis activator ML210, and treatment with the ferroptosis inhibitor liproxstatin-1 significantly reversed the suppressive effect of PRDX1 knockdown on xenograft tumor growth. Mechanically, PRDX1 deletion triggered ferroptosis in B-ALL cells by inhibiting the cAMP pathway. PRDX1 deficiency modulates ferroptosis in B-ALL cells by blocking the cAMP pathway, which offer a novel perspective on the pathogenesis of B-ALL.

Here, we reported a doxorubicin (DOX)-Fe complex and RSL3 co-loaded liposomes (DOX-Fe/RSL3@LIPs) for ferroptosis-enhanced chemotherapy on TNBC tumors. The tumor cell ferroptosis was observably enhanced via supplements of the ferrous ions and H2O2, and RSL3-derived GPX4 inhibition to severely destroy the oxidation balance in cells. In this paper, the DOX-Fe/RSL3@LIPs have exerted a synergistic anticancer effect on TNBC by combining ferroptosis and conventional chemotherapy, and made a meaningful exploration of new strategies for TNBC therapy.

The CHPT1-pSTAT3-SLC7A11 axis governs ferroptosis-dependent chemoresistance in PDAC. Dual targeting of CHPT1 and ferroptosis pathways represents a promising strategy to overcome GEM resistance, highlighting metabolic-kinase crosstalk as a therapeutic vulnerability.

The ferroptosis inducer erastin also inhibits melanoma growth. Combining the ATAD2 inhibitor BAY-850 with the MEK inhibitor trametinib potently suppresses melanoma growth. Our study identifies ATAD2 as a key driver of melanoma and provides a rationale for targeting ATAD2 in conjunction with the MAPK pathway to treat melanoma.

Mechanistic studies using cycloheximide chase assays, Wnt pathway modulators (LiCl, SKL2001, and Salinomycin), and protein interaction analyses demonstrated that KCNJ12 stabilizes β-catenin through the physical interaction with lipoprotein receptor-associated protein 6 (LRP6), disrupting AXIN/APC/GSK-3β complex assembly and subsequent proteasomal degradation...Our findings establish KCNJ12 as a novel Wnt/β-catenin regulator and propose dual therapeutic strategies against HCC-mediated chemoresistance: pharmacological suppression of KCNJ12 channel activity and targeted disruption of KCNJ12-LRP6 protein interactions. This mechanistic framework advances our understanding of stemness regulation in HCC and provides feasible targets for developing next-generation anti-HCC therapies.