These findings may explain one of the reasons for the suboptimal efficacy of simvastatin in the treatment of pancreatic cancer, while also providing new insights for research on the antitumor effects of statins.

Moreover, USP18 silencing promoted the accumulation of lipid reactive oxygen species (ROS), malondialdehyde (MDA), and Fe2+, thereby enhancing erastin-induced ferroptosis...Subsequent rescue experiments confirmed that the tumor-promoting effects of USP18 were abrogated upon HDAC3 knockdown. Taken together, our results identify the USP18/HDAC3 axis as a key regulator of EC cell proliferation and ferroptosis suppression, underscoring the potential of USP18 as a therapeutic target in EC.

To better target the CD44-expressing breast cancer cells, we report the design and synthesis of a new nanodrug, G2-Sal-ICG, comprising a hyaluronan (HA)-like polysaccharide (G2) conjugated with the anticancer drug salinomycin (Sal) and the imaging agent indocyanine green (ICG)...In vivo experiments with an orthotopic breast cancer model demonstrated the superior tumor-targeting capability of G2-Sal-ICG and its ability to significantly suppress tumor growth. Our findings suggested G2-Sal-ICG is a promising theranostic nanodrug for CD44-targeted therapy, combining efficient drug delivery with real-time non-invasive imaging, thus highlighting its potential for clinical applications in breast cancer treatment.

The combination of brusatol with RAS-selective lethal 3 (RSL3) significantly enhanced ferroptosis in NPC cells, accompanied by increased levels of cellular reactive oxygen species (ROS) and lipid peroxidation. These effects were further confirmed in NPC xenograft mouse models, as demonstrated by reduced tumor volumes, decreased Ki-67 and Nrf2 staining, and increased expression of cyclooxygenase-2 (COX2). In conclusion, brusatol promotes ferroptotic cell death in NPC cells by inducing Nrf2 degradation and enhancing lipid peroxidation, suggesting its promising therapeutic potential for the treatment of NPC.

Our study successfully isolated SCRENs from Smilax china rhizomes and demonstrated their inhibitory effects on HCC cell proliferation, migration, and invasion through in vitro cellular experiments. Mechanistic investigations revealed that SCRENs mediate their anti-tumor effects primarily through modulation of mitophagy-associated ferroptosis via GPX4/ACSL4 axis.

SLC7A11 knockdown regulates intracellular redox balance through the GSH-GPX4 axis, thereby promoting cellular cuproptosis. Targeting SLC7A11 can enhance the sensitivity of CRC cells to copper ionophores and may represent a novel therapeutic strategy to enhance cuproptosis of CRC cells.

Combining ibrutinib with the GPX4 inhibitor RSL3 enhances ferroptosis and improves antileukemic efficacy in vivo. Notably, ACSL1 is selectively upregulated in U-CLL cells and represents a targetable metabolic enhancer of ferroptosis sensitivity, as shown in vivo. Our findings reveal that TFRC and ACSL1 are functionally distinct yet targetable nodes that govern ferroptosis vulnerability in CLL patients and may guide novel therapeutic strategies for high-risk patients.

Ferrostatin-1 or Erastin successfully reversed the phenotype triggered by HSP27 alterations. HSP27 can induce the growth of CSCC by inhibiting ferroptosis, and is expected to become a new target for the treatment of CSCC.

MAMs were isolated from NCI-H295S cells treated with mitotane, the ferroptosis inducer RSL3, or control. In conclusion, locally reduced Q10 in MAM may contribute to impaired respiratory chain activity and free radical excess induced by mitotane. Recruitment of GRIPAP1 protein to MAMs may transduce cell death.

Co-treatment with the tankyrase inhibitor XAV-939 and RSL3 enhanced growth inhibition of eCCA cells, indicating that WNT signaling contributed to ferroptosis resistance. These findings indicate that iCCA exhibits a preferential dependency on GPX4, whereas WNT-β-catenin signaling mediates resistance in eCCA. Collectively, the results clarify the molecular basis of subtype-specific ferroptosis vulnerability and offer a rationale for combinatorial therapeutic strategies that integrate GPX4 and WNT pathway inhibition when treating refractory eCCA.

Our findings highlight RSL3 as a promising therapeutic agent and STAT3 as a potential target for treating PARPi-resistant breast cancer.

Our findings highlight ferroptosis induction as a promising antitumor mechanism in mesothelioma, particularly in the epithelioid subtype. While GPX4 inhibitors such as RSL3 are effective in vitro, further studies are needed to overcome pharmacological limitations and define molecular determinants of ferroptosis susceptibility, which may inform future personalized therapeutic strategies.