Targeting Kras-mutant Lung Adenocarcinoma Tumors Through Il-1ß Inhibition

Lung adenocarcinoma (LUAD) often carries activating KRAS mutations, making tumours aggressive and therapy-resistant. KRAS signalling amplifies IL-1β-driven NF-κB and a CCL2/VCAN chemokine loop, shaping a pro-tumour microenvironment. We therefore asked whether Isunakinra—a potent IL-1-receptor antagonist—could break this circuit. We built a bioluminescent NF-κB reporter (NF-κB.GFP.Luc, pNGL) and introduced it into four KRAS-mutant (LLC, MC38, AE17, FULA1) and two wild-type (B16F10, PANO2) murine lines. IL-1β sharply increased reporter output; co-treatment with Isunakinra suppressed NF-κB far more in mutant than wild-type cells (p