Fig. 7. Triple combination inhibiting GPX4, cystine uptake and transsulfuration eliminates MYCN-amplified tumors in vivo.
a, Regulation of pro- and anti-ferroptotic players by oncogenic MYCN in MYCN-amplified neuroblastoma cells that may trigger ferroptosis when both cysteine and GSH availability is limited. Therapeutic intervention points are indicated in green. b, Dosage scheme applied with either double (IKE/PPG) or triple combination (GPX4 knockout, IKE and PPG). c,d, Tumor weight after combination treatment with IKE and PPG (n = 5 mice per group; c) and the triple combination of GPX4 reduction plus IKE/PPG treatment (n = 9 in the control group and n = 12 mice in the treated group; d). e, Representative photographs of fully grown tumors in the vehicle group versus residual tumors after triple combination. f, Transcriptional changes of ferroptosis markers after GPX4 reduction plus IKE/PPG in residual tumor tissue (n = 5 tumor samples from each group). Statistical analysis was performed using a one-tailed Student’s t-test for the in vivo experiments. Box plots: the center line indicates the median value and the lower and upper hinges represent the minimum and maximum points. Each dot corresponds to one sample; P values as indicated. Panels a and b created with BioRender.