NCOA4 (Nuclear Receptor Coactivator 4)

Importantly, we demonstrate that Pinostilbene significantly enhances the sensitivity of lung cancer cells to RSL3-induced ferroptosis...Furthermore, Pinostilbene enhances antitumor immunity by upregulating inflammatory cytokines and promoting the infiltration and activation of tumor-killing CD8+ T cells, alongside drving anti-tumor M1 polarization of macrophages. Our study highlights the potential of Pinostilbene as a promising therapeutic agent for NSCLC, offering a multifaceted mechanism of action through ferroptosis sensitization and immunostimulation.

Elbasvir targets NCOA4-FTH1 to induce ferroptosis, offering a repurpose strategy for ESCC. Its safety profile supports clinical translation, with potential applications in iron metabolism-dependent cancers.

Furthermore, the review elaborates on the clinical efficacy of highly selective RET inhibitors (selpercatinib and pralsetinib), including their breakthroughs in pediatric patients and radioactive iodine-refractory cases. Primary and acquired resistance mechanisms (on-target mutations, bypass activation) and corresponding strategies (next-generation inhibitors, combination therapies) are also analyzed. By integrating recent advances in basic and clinical research, this review provides a comprehensive reference for the precision diagnosis and treatment, mechanistic investigation, and drug development for RET fusion-positive PTC.

This study demonstrates that dandelion extract induces ferroptosis in TNBC cells both in vitro and in vivo by regulating ferritinophagy mediated by the NCOA4-FTH1 axis, thus suggesting novel therapeutic strategies for TNBC treatment.

Beclin1 knockdown and DHODH overexpression can reduce DOX-induced liver injury by preventing ferroptosis and autophagy.

RET fusion-positive LUAD comprises biologically heterogeneous subsets defined by fusion partners. KIF5B-RET tend to occur at earlier stages, whereas non-KIF5B are more frequently associated with CDKN2A co-mutations and may derive greater benefit from selective RET inhibition. Immunochemotherapy demonstrates comparable efficacy regardless of fusion partner, highlighting the need for partner-specific therapeutic strategies in RET fusion-positive LUAD.

Overexpression of SREBP1 attenuated BPNS-induced ferroptosis, confirming its critical role. These findings suggest that BPNSs induce ferroptosis in OSCC via the PI3K-AKT-SREBP1 signaling pathway, providing a novel therapeutic strategy for OSCC treatment.

This study suggests that CRO may reduce ferritinophagy-induced colonic oxidative damage in rats via modulating AKT/mTORC1/ULK1. Ferritinophagy as an attractive therapeutic target in different experimental and clinical conditions deserves further investigation.

Que exerts significant antitumor effects in NSCLC by targeting EIF3D to activate NCOA4-mediated ferritinophagy and ferroptosis. This study reveals a novel mechanism involving the EIF3D-NCOA4 axis in the regulation of ferritinophagy-dependent ferroptosis, providing a potential therapeutic strategy for the treatment of NSCLC.

In acute myeloid leukemia (AML), evidence suggests that leukemic stem cells rely more heavily on iron-driven mitochondrial metabolism, making ferritinophagy a potential therapeutic target. This review summarizes current knowledge of NCOA4 regulation and ferritinophagy, discusses their relevance in hematologic malignancies, and highlights therapeutic opportunities and unresolved questions in AML.

Our findings positioned kitasamycin as a promising adjunct to immunotherapy for cancer patients requiring concurrent antibiotic therapy. Abbreviations: FTH1: ferritin heavy chain 1; ICB: immune checkpoint blockade; IFNG: interferon gamma; mIHC: multiplex immunohistochemistry; scRNA-seq: single-cell RNA sequencing.