SLC7A11 (Solute Carrier Family 7 Member 11)

Treatment with the PI3K inhibitor LY294002 produced changes consistent with those observed upon YBX1 silencing. In a subcutaneous xenograft mouse model, YBX1 silencing was associated with reduced tumor growth and ferroptosis-related changes, effects that were partially reversed by EGF treatment. These findings suggest that YBX1 is associated with ferroptosis-related changes and altered proliferation and migration in A549 cells, potentially involving PI3K/AKT/mTOR signaling, highlighting YBX1 as a potential therapeutic target.

ACLY-derived acetyl-CoA enhances H3K27 acetylation (H3K27ac) modification level in the promoter of SLC7A11 gene, ultimately enhancing SLC7A11 transcription and ferroptosis resistance. Collectively, our study provides a mechanistic understanding of the interplay between ferroptosis resistance and lymph node metastasis, providing a possibility to combat lymph node metastasis in cervical cancer.

Interestingly, we demonstrated that Almonertinib-activated autophagy directly participates in ferroptosis activation by promoting Fe2+ release upstream and influencing lipid peroxidation, elucidating the occurrence of autophagy-dependent ferroptosis. In summary, these findings indicate that Almonertinib suppresses liver cancer progression by inducing autophagy-dependent ferroptosis in HepG2 and MHCC-97H cells, potentially providing insights for positioning Almonertinib as a novel therapeutic candidate for future liver cancer treatment.

ORC1 represents a promising therapeutic target, as its inhibition induces replication stress, cell cycle arrest, and enhances sensitivity to existing chemotherapeutic agents. Future research should focus on developing specific ORC1 inhibitors and exploring their synergistic potential with immunotherapy and targeted therapies.

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.

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.

This study pioneers a dual-functional scaffold hybridization strategy, merging synthetic innovation with ferroptosis induction to overcome resistance. The robust efficacy, mechanistic clarity, and superior safety profile of 3e and 4d position them as transformative candidates for metastatic melanoma therapy, offering a novel approach to combat drug resistance and toxicity barriers.

Furthermore, different radiotherapy fractionation regimens induce varying degrees of ferroptosis. Increasing single-fraction radiation doses can enhance lipid peroxidation and ferroptosis, suggesting a promising research direction for combining hypofractionation radiotherapy with ferroptosis inducers (FINs).

Finally, NOS2 knockdown using siRNA also showed enhanced expression of ferroptosis markers which is the same response observed with the treatment of the compounds. In conclusion, this study suggests that fungal endoperoxide-containing steroids from D. confragosa represent new ferroptosis inducers via targeting NOS2, supporting their potential as anticancer drug candidates.

Mechanistic nodes (SLC7A11, GPX4, PRMT5, ATF4/NUPR1) and stromal/macrophage circuits link ferroptosis resistance to immune evasion. Emerging strategies combine ferroptosis induction with checkpoint blockade, adoptive cellular therapies, nano-delivery, and microenvironment reprogramming to convert "cold" disease into durable responders.