RSL3

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.

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.

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.

Fibroblast membrane engineering, combined with chemokine-gradient navigation and photothermally controlled therapeutic activation, represents the translational potential of nanomedicine in clinical by developing precision nanomedicines that coordinate biological recognition with stimulus-responsive bioactivity.

Our research may provide intervention strategies for the treatment of OV.

To address this, we developed a novel nanomedicine, GSH-depleted and ferroptosis-induced (FiN), designed to encapsulate and deliver the GPX4 inhibitor RSL3, resulting in a dual ferroptosis-induced nanomedicine (DFiN). Both in vitro and in vivo experiments confirmed that DFiN is effective in overcoming gemcitabine resistance in GR PDAC cells and PDX tumors, with minimal toxicity observed. This study presents a promising strategy for addressing drug resistance in cancer therapy.

A triple therapy combining CH-223191, ferroptosis inducer (Imidazole ketone erastin or RSL3), and anti-PD-1 agent demonstrates superior efficacy and safety in vivo. Together, our findings demonstrate that IL4I1⁺ TAMs and TDO2⁺ myCAFs synergistically establish an immunosuppressive, ferroptosis-resistant niche via AhR signaling in solid predominant LUAD and offer promising therapeutic strategies to reprogram the tumor microenvironment.

PS-MPs promote NPC progression by generating mitochondrial ROS that activate the NRF2-SLC7A11/GPX4 antioxidant axis and suppress ferroptosis. Pharmacologic reactivation of ferroptosis counteracts these effects, highlighting ferroptosis-targeted therapy as a potential strategy for mitigating microplastic-associated cancer risk.

Notably, SLC38A5 depletion sensitizes CRC cells to RSL3-induced ferroptosis...Our findings reveal a novel mechanism wherein SLC38A5 confers ferroptosis resistance in CRC via YAP nuclear translocation within the Hippo signaling pathway. Collectively, this study highlights SLC38A5 as a potential therapeutic target to enhance ferroptosis-based cancer therapy, offering new strategies to improve CRC treatment outcomes.