GPX4 (Glutathione Peroxidase 4)

Genetic studies identify SLC7A11 as a critical mediator: its knockdown sensitizes cells to the combination, while its overexpression confers resistance. These findings establish a novel ferroptosis-based mechanism for the PTX/SUN synergy, positioning SLC7A11 as a key determinant of therapeutic response and providing a rationale for targeting this pathway in lung cancer.

PRELID2 promotes NPC by upregulating TXNDC12 to sustain GSH levels, thereby enhancing GPX4 activity, inhibiting ferroptosis, and driving tumor growth. Suggest PRELID2 as a potential prognostic biomarker and therapeutic target for NPC.

Pharmacologic targeting of NDUFS4 using the niclosamide analog ARVib-7 phenocopied genetic depletion, suppressing mitochondrial respiration and enhancing olaparib efficacy to inhibit the growth of resistant spheroids. These findings identify NDUFS4 as a key mediator of PARPi resistance and a therapeutic vulnerability in advanced prostate cancer. Targeting NDUFS4 disrupts oxidative phosphorylation and induces ferroptosis, providing a strong rationale for combination strategies with PARP inhibitors to overcome drug resistance.

In summary, we present a targeted nanoplatform that enhances the antitumor efficacy of Apa at lower dosages by leveraging ferroptosis induction. This strategy holds promise for improving the clinical outcomes in patients with GC.

This molecular targeting presents a promising therapeutic avenue to preserve BII and potentially improve long-term implant survival in bone cancer patients. In this mini-review, we summarized the effects of ferroptosis on orthopedic implants, highlighting the potential of ferroptotic-targeting treatment to improve long-term implant outcomes in patients undergoing oncologic reconstruction.

A series of in vitro and in vivo studies demonstrate that Pd/s-CALDH@Palbo suppresses pan-ERBB pathway activation and GPX4 overexpression, reduces cellular metabolism, and triggers apoptosis and ferroptosis, thereby effectively overcoming CDK4/6 inhibitor resistance and demonstrating potent antitumor efficacy in OSCC. Overall, our work presents a nanozyme-mediated drug repurposing paradigm, with potential applications in precision medicine.

To overcome this, we developed a synergistically enhancing ferroptosis nanomedicine named sorafenib (SOR)-quercetin (QUE) nanoparticles (SQ NPs) by co-assembling SOR, QUE, and polyvinylpyrrolidone K30 (PVP K30)...In vivo studies on antitumor and antimetastatic effects have demonstrated the superior therapeutic efficacy and metastasis-inhibiting capabilities of SQ NPs in the context of TNBC. This report highlights the therapeutic potential of QUE in synergy with SOR under hypoxic conditions, offering a novel strategic approach for the treatment of TNBC.

SSD inhibits the malignant phenotype of BCa by targeting PI3K/AKT to trigger ferroptosis. Its synergistic effect with GEM from the dual mechanisms of ferroptosis sensitization and epithelial-mesenchymal transition inhibition, providing an innovative combination strategy based on natural product active ingredients to overcome bladder cancer chemoresistance.

Furthermore, in vitro and in vivo experiments validate the ability of the small molecule filgotinib, identified by D-FR20, to re-sensitize BBDI and effectively eliminate resistant TNBC cells. Collectively, this study provides two computational frameworks for predicting BBDI resistance and candidate re-sensitizer, as well as demonstrates the roles of ferroptosis in BBDI resistance, offering a promising avenue for TNBC treatment.

This study establishes TKFC as an endogenous ferroptosis regulator and direct molecular target of Icaritin in HCC, positioning it as both a prognostic biomarker and therapeutic target for precision therapy.

Furthermore, CDDO-Me did not compromise the antitumor efficacy of DOX/LAP in breast cancer cells. CDDO-Me protects against DOX/LAP-induced cardiotoxicity by stabilizing GPX4 and inhibiting ferroptosis, offering a promising therapeutic strategy that preserves cardiac function without interfering with chemotherapy.

The combination of SNB and FEN represents a promising multi-targeted therapeutic approach against GB. SNB and FEN combination capable of modulating and reprogramming key molecular pathways involved in GB progression and MDR.