Overview

• Chemotherapy-induced pyroptosis in bladder tumors triggers caspase-1–mediated inflammatory signals that undermine treatment efficacy.
• These inflammatory signals reprogram αSMA+ fibroblasts into collagen-III–rich iCAFs that nurture chemoresistant cancer stem cells.
• Belnacasan, a selective caspase-1 inhibitor, blocks this pyroptosis-driven inflammation and halts collagen production by converted fibroblasts.
• Combining belnacasan with standard chemotherapy in mouse models restores drug sensitivity and markedly slows tumor growth.
• Researchers are now extending studies to breast and other cancers and preparing early-phase clinical trials of the combination therapy.