Fibrotic remodeling of tissues and tumors establishes immunosuppressive microenvironments that drive organ dysfunction and, in cancer, limit response to immunotherapy. Senescent-like cells are conserv...

Optimized SORT LNPs enable precise and long-lasting base editing in dual organs in a disease mouse model.

Aqueous nanotube-catalysed Fenton chemistry enables handle-free attachment of chemically diverse small molecules to single-walled carbon nanotubes, generating tunable sp3 quantum-well defects and reds...

Aqueous nanotube-catalysed Fenton chemistry enables handle-free attachment of chemically diverse small molecules to single-walled carbon nanotubes, generating tunable sp3 quantum-well defects and reds...

npj Biomedical Innovations - Engineering macrophages for cancer immunotherapy: emerging insights and therapeutic potential

A protocol to isolate small intracellular vesicles from human cells is reported; these are molecularly distinct from small extracellular vesicles and show superior therapeutic potential in retinal deg...

Learn about a blood test using carbon nanotubes that could potentially detect brain tumors.

Nanoparticles targeted to solid tumor vasculature improve the pharmacologic properties of PROTACs.

Nanoparticles targeted to solid tumor vasculature improve the pharmacologic properties of PROTACs.

At a moment when large-scale resistance can feel futile,
there are other ways to oppose, engage, and fight back.

Although ferroptosis resistance is prevalent among many cancer cell types, precisely how ferroptosis surveillance mechanisms are induced remains elusive due to the heterogeneity of the cellular mutational status and metabolic states. Here, we find that phospholipase PAFAH2 regulates ferroptosis through its unique ability to specifically detoxify membrane-bound oxidized phospholipids in KEAP1 mutant and NRF2-active cancer cells. We show that the genetic or chemical perturbation of PAFAH2 is sufficient to sensitize KEAP1 mutant lung adenocarcinoma cells to ferroptosis. Lipidomic analyses reveal that PAFAH2 inhibition shifts the cellular lipidome to a distinctly ferroptosis state characterized by the enrichment of key phospholipids previously identified to be important in ferroptosis, like ether-linked phosphatidylethanolamines. Finally, we comparatively assessed the antitumor efficacy of PAFAH2 inhibitor monotherapy versus cotreatment with a nanoparticle-stabilized GPX4 inhibitor formulation. Our findings support that the broad applicability of PAFAH2 inhibition can be used in ferroptosis induction and abrogation of ferroptosis resistance across cancer types.

The following column by Senator Todd Young (R-Ind.) and Matthew Pottinger, Former Deputy National Security Advisor of the United States, was published in The Washington Post on March 24, 2025. By Sena...