Using rat spinal cord neurons in vitro, we found that erastin increased levels of Fe2+, RIG-I, and CCL5, effects that were reversed by the iron chelator deferoxamine. Intrathecal administration of deferoxamine or RIG-I siRNA attenuated pain behaviors and downregulated the expression of both RIG-I and CCL5. These findings demonstrate the spinal Fe2+/RIG-I/CCL5 pathway as a critical promoter of BCP and highlight the potential therapeutic strategies targeting iron chelation or RIG-I signaling.

Our findings reveal a novel miR-214-3p/GPX4/ferroptosis axis in OSCC DDP resistance. miR-214-3p suppresses GPX4 to promote ferroptosis, thereby reversing DDP resistance. This study identifies miR-214-3p as a potential therapeutic target for overcoming chemoresistance in OSCC by modulating ferroptosis.

Our studies might offer insights for the application of ferroptosis or macrophage polarization in the therapy of OSCC.

Significantly, Erastin-a SLC7A11 inhibitor-overcame YBX1-mediated resistance, synergizing with 5-Fu to induce ferroptosis and suppress tumor growth. Collectively, we unveil the ODC1-YBX1-SLC7A11-ferroptosis axis as a central mechanism of chemoresistance in STAD. Targeting this axis-via ODC1 inhibition or ferroptosis induction-represents a novel therapeutic strategy to reverse treatment resistance in gastric adenocarcinoma.

Notably, pitavastatin calcium synergized with the ferroptosis inducer RSL3 to enhance ferroptotic activity and suppress HNSCC progression. These findings delineate a TRAPPC4-FOS-TRIM55-GPX4 signaling axis that drives ferroptosis resistance and tumor progression and highlight TRAPPC4 as a promising therapeutic target for ferroptosis-based intervention in HNSCC.

Lipophagy can promote RAS-selective lethal 3 (RSL3)-induced ferroptosis. LAPTM5 enhanced the sensitivity of glioma cells to ferroptosis inducer erastin, while suppression of lipophagy inhibited LAPTM5-mediated sensitization to erastin. The finding that glioma cells with high LAPTM5 expression were more sensitive to ferroptosis inducers suggests that glioma patients with high LAPTM5 expression may be more responsive to ferroptosis-inducing therapies.

Moreover, NheA-O activity synergizes with RSL3, and NheA-O mediated cell death is antagonized by Fer-1, indicating the role of NheA-O in inducing ferroptosis-like cell death. Overall, these results describe NheA-O as a novel therapeutic agent to combat tumorigenesis by targeting tumor cell membrane and proteasomal degradation of GPX4 to trigger ferroptosis-like cell death and expands the paradigm of tumoricidal protein-lipid complexes functionality across biological kingdoms.

Here, we identify EBV latent membrane protein 1 (LMP1), a key viral oncogene necessary for B cell immortalization and which mimics aspects of CD40 signaling, drives resistance to ferroptosis induction by erastin, a small molecule that blocks cystine uptake...PFKFB4 was also necessary for LMP1-mediated Burkitt B cell ferroptosis resistance. Collectively, these results identify PFKFB4 as a key host cell EBV metabolism remodeling target critical for infected B cell redox defense.

Interestingly, chemotherapy-resistant cancer cells can be induced to undergo ferroptosis, prompting our investigation into RSL3, a potent ferroptosis inducer, in MSS CRC cells...Notably, the combination enhanced the antitumor response of anti-PD1, a treatment otherwise ineffective on this tumor. These findings suggest that targeting HIF-1α represents a promising therapeutic strategy when used in conjunction with a ferroptosis inducer for the treatment of MSS CRC.

Ferroptosis induction by RSL3/FIN56 led to increased TFR1 expression and ROS generation...Temozolomide in combination with siRNA-mediated gene silencing showed a significantly higher antitumor effect than the drug or silencing alone. This may be one of the important therapeutic vulnerabilities of GBM. High TFR1 expression was associated with shorter overall survival in all gliomas together but not in GBM separately.

However, PRDX4 overexpression showed opposite effects, which were partly reversed by the ferroptosis inhibitor, ferrostatin-1 and the inducer erastin. Most crucially, PRDX4 depletion-mediated inactivation of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway could be rescued by 740 Y-P (a PI3K activator), whereas PRDX4 overexpression triggered the activation of the PI3K/AKT signaling pathway, which could be reversed by the PI3K inhibitor LY294002. Collectively, the data suggest that PRXD4 suppresses ferroptosis in ESCC cells by activating the PI3K/AKT signaling pathway, suggesting that targeting PRDX4 may be a novel strategy for treating patients with ESCC.

Clinically, genetic silencing of UBE2C induces ferroptosis and sensitizes tumor cells to the ferroptosis inducer erastin, revealing a therapeutically exploitable vulnerability in MYCN-amplified malignancies. Our study reveals a previously unrecognized MYCN-UBE2C-TFRC-ferroptosis regulatory axis that drives neuroectodermal tumor growth. These findings establish a mechanistic rationale for combining UBE2C silencing and ferroptosis induction as a precision therapeutic strategy against MYCN-amplified tumors.