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.

Here we demonstrate that macrophages co-cultured with ferroptotic cancer cells from various types effectively mitigate cell death induced by GPX4 inhibitors (RSL3 and ML162), GPX4 silencing via shRNA, or the Xc- system inhibitor IKE...Furthermore, in placental villi explants, macrophages protect trophoblasts from ferroptotic death. These results underscore the intricate interplay between ferroptotic cells and their microenvironment and provide compelling evidence of a yet-unrecognized anti-ferroptotic activity of macrophages as a cell-extrinsic mechanism that could be exploited by cancer cells to escape ferroptosis.

In the autophagy mediated by copper and erastin (a ferroptosis inducer), the autophagy receptors TAX1BP1 and SQSTM1 can promote the degradation of GPX4, effectively reducing the resistance of cancer cells to ferroptosis...In this review, we conduct a comprehensive and in-depth analysis of the roles played by selenoproteins derived from selenium metabolism in the regulation of immune cells associated with immune diseases. Moreover, we elaborate in detail on the effects of GPX4 in relation to ferroptosis in solid tumors under the influence of autophagy-mediated immunomodulation.

In line with this, HnRNPU deletion induced ferroptosis and increased sensitivity to RSL3 treatment and cysteine deprivation...Findings demonstrate that HnRNPU promotes proliferation and inhibits ferroptosis by regulating the mRNA stability of SLC7A11 and SLC3A2. Targeting HnRNPU is a potential therapeutic approach for COAD treatment.

Moreover, SLC7A11 inhibitors, particularly sulfasalazine and erastin, effectively reversed resistance, in 18 clinical trials (Phase I-III) completed over the last decade. Targeting SLC7A11 presents a promising therapeutic strategy to modulate redox balance, metabolism, and ferroptosis, towards efficient cancer treatments.

Knockdown of GPX4 by RNAi reversed the resistance of PTEN-deficient PC3 and LNCaP cells to Erastin. Collectively, our findings suggest that ferroptosis can serve as a potential therapeutic strategy for prostate cancer, and PTEN status may influence cellular sensitivity to ferroptosis.

Furthermore, the ferroptosis inducer RSL3 synergized with cisplatin to enhance ferroptosis and mitochondrial fragmentation, effectively sensitizing ACTG1-overexpressing cells both in vitro and in xenograft models. Our findings establish ACTG1 as a critical mediator of cisplatin resistance in NSCLC through regulation of mitochondrial integrity and ferroptosis. Targeting the ACTG1-MFN2 axis combined with ferroptosis induction represents a promising therapeutic strategy to overcome cisplatin resistance.

Importantly, ACSL6 knockdown increased GPX4 expression and colony growth, partially rescuing DHA-induced suppression, whereas ACSL6 overexpression enhanced DHA-mediated GPX4 reduction and colony inhibition, effects reversible by RSL3 or ferrostatin-1...In vivo, DHA supplementation potentiated oxaliplatin-suppressed tumor growth in tumors with upregulated ACSL6 expression, accompanied by GPX4 reduction. Together, these findings highlight ACSL6 as a critical determinant of DHA sensitivity in cancer, underscoring its potential as a predictive biomarker for chemotherapy-DHA combination strategies. By modulating key metabolic and signaling pathways, ACSL6 could influence cellular susceptibility to ferroptosis and may guide therapeutic approaches that enhance chemotherapy through DHA supplementation.

This study highlights the potential role of PPIA as a critical oncogenic driver in liver cancer, suggesting that targeting PPIA could offer therapeutic advantages in the treatment of this malignancy.