Roughly half of pancreatic cancer patients have comorbid diabetes, which worsens survival. This study reveals why: diabetes drives tumor endothelial cells into senescence, causing them to secrete INHBB—a TGF-β superfamily member—that fuels tumor growth via a senescence-associated secretory phenotype (SASP). Using mouse models combining high-fat diet and streptozotocin to mimic type 2 diabetes, researchers showed that diabetic tumors harbor more senescent endothelial cells with elevated INHBB. Notch signaling regulates INHBB production. Blocking its receptor (ActRII) with the monoclonal antibody bimagrumab significantly slowed tumor progression in diabetic mice, and combining bimagrumab with metformin produced synergistic antitumor effects without meaningfully altering blood glucose.
