'Fiery' Cell Death During Chemotherapy May Drive Bladder Cancer Resistance

Recent research from Houston Methodist reveals that the inflammatory response triggered by chemotherapy, specifically a form of cell death called pyroptosis or 'fiery death,' may inadvertently contribute to bladder cancer's resistance to treatment. Traditionally, chemotherapy aims to eliminate cancer cells; however, this study demonstrates that the process of pyroptosis can activate support cells within the tumor, known as fibroblasts, causing them to produce collagen. This collagen provides a protective environment for cancer stem cells, enabling them to survive treatment and potentially leading to recurrence.

The investigation, detailed in the publication "Caspase-1–dependent pyroptosis converts αSMA+CAFs into collagen-III high iCAFs to fuel chemoresistant cancer stem cells" in Science Advances, utilized mouse models and patient samples for analysis. The researchers found that blocking this inflammatory pathway with the drug belnacasan could reduce collagen production, thereby improving the effectiveness of chemotherapy.

Notably, not all forms of cell death are beneficial in cancer treatment. The study emphasizes that the inflammatory type of cell death associated with pyroptosis may promote tumor survival instead of eradication. Dr. Hongbo Gao and Dr. Keith Syson Chan explained that this inflammatory response creates a microenvironment conducive to cancer stem cell survival, fueling resistance.

Therapeutically, combining standard chemotherapy with inhibitors like belnacasan holds promise for overcoming resistance in bladder cancer. The research suggests that targeting the inflammatory processes initiated during pyroptosis could enhance treatment outcomes. While further studies are needed across different tumor types, initial evidence indicates similar strategies might benefit other cancers, including breast cancer.

This discovery underscores the complexity of cancer biology and highlights the importance of understanding immune responses during cancer therapy. Modulating these reactions could lead to more effective treatment protocols and reduce recurrence rates in bladder cancer patients.

Source: https://medicalxpress.com/news/2025-07-fiery-cell-death-chemotherapy-bladder.html