ACSL4 (Acyl-CoA Synthetase Long Chain Family Member 4)

DS extract alleviates TRZ-induced cardiotoxicity, manifested by improved cardiac function, reduced myocardial injury markers, and mitigated tissue and mitochondrial damage. Its mechanism of action is associated with regulating proteins in the ferroptosis pathway (upregulating GPX4 and downregulating ACSL4). Additionally, tanshinone I, IIA, and IIB have been identified as potential active components.

Future directions include biomarker validation, optimization of drug delivery, early-phase clinical trial development, and multidisciplinary collaboration to balance ferroptosis induction in tumors while protecting normal tissues. Collectively, ferroptosis is emerging as both a vulnerability and a therapeutic opportunity for improving outcomes in NPC.

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.

This study elucidates a novel HDAC1/HIF1α/CA9 axis through which Apatinib induces ferroptosis. Targeting this pathway offers translational potential for overcoming Apatinib resistance in GC therapy.

To overcome these limitations, we propose a senescence-primed ferroptosis strategy using a metal-organic framework (MOF)-based nanoplatform (ZPG) that codelivers CDK4/6 inhibitor (palbociclib) and ferroptosis inducer (gallium ions, Ga3+) to enhance antitumor efficacy...Leveraging ZPG for the codelivery of therapeutic agents, the synergistic mechanism resulted in markedly enhanced antitumor efficacy both in vitro and in vivo, with minimal off-target toxicity. Collectively, the ZPG-enabled senescence-primed ferroptosis strategy provides a promising and mechanistically rational approach for improving cancer therapy.

In conclusion, our findings demonstrate that Mos mitigates SAP progression by inhibiting ferroptosis and inflammatory responses via targeting KEAP1, blocking NRF2 degradation, and activating the NRF2/HO-1 pathway. This study provides novel insights into ferroptosis-targeted therapeutic strategies for SAP and offers experimental evidence supporting the use of dendrobium-derived compounds in the treatment of acute pancreatitis.

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.

Harmine exerts antitumor effects in NSCLC by inducing ferroptosis through direct targeting of PDE4D and suppression of the PI3K-Akt-Nrf2 pathway, highlighting PDE4D as a novel therapeutic target and harmine as a promising candidate for NSCLC treatment.

Moreover, these effects were partially reversed by the ferroptosis inhibitor Ferrostatin-1. Collectively, these results indicate that α-Hederin exerts antitumor effects against osteosarcoma by inducing ferroptosis and impairing mitochondrial function, partly through inhibition of the PI3K/AKT signaling pathway, providing a potential therapeutic strategy for osteosarcoma.

Moreover, the correlation of PPARs with ACSL4 highlights the possible role of PPAR-α and PPAR-γ in the regulation of tumor tissue ferroptosis and suggests that targeting these pathways could offer new therapeutic strategies for managing breast cancer. However, further studies are needed to understand the mechanism of action.

Emerging therapeutic strategies targeting redox-sensitive nodes, including GPX4 degraders, mitophagy inducers (urolithin A) and chronotherapy, have the potential to overcome resistance. By elucidating the crosstalk between mitochondrial quality control and ferroptotic signaling, the present review provides a mechanistic framework for precision oncology in EC, emphasizing subtype-specific vulnerabilities and spatiotemporal redox profiling.

Clinically, the identified ferroptosis-related signatures offer potential as predictive biomarkers for metastatic risk, and ferroptosis induction emerges as a promising therapeutic strategy for metastatic PCa. Future research should focus on exploring the crosstalk between ferroptosis and other cancer-related pathways to develop more effective targeted therapies.