A new study from Houston Methodist reveals a surprising twist in the fight against bladder cancer: a type of cancer cell death triggered by chemotherapy may actually make the cancer harder to treat.
This research helps explain why some bladder cancers become resistant to chemotherapy and offers a potential solution that could improve treatment outcomes.
Chemotherapy is designed to kill cancer cells, but this study shows that one form of cell death it causes—called pyroptosis, or “fiery” death—may trigger an inflammatory response that unintentionally helps cancer survive.
Published in the journal Science Advances, the research shows that instead of completely destroying the tumor environment, chemotherapy can cause surrounding support cells, called fibroblasts, to change their behavior.
Instead of dying off, some of these fibroblasts begin producing a type of collagen that supports cancer stem cells—the toughest, most treatment-resistant cancer cells.
This collagen-rich environment gives the cancer stem cells what they need to survive and even grow stronger against chemotherapy.
Dr. Hongbo Beth Gao, one of the study’s lead authors, explained that not all cell death is beneficial when it comes to fighting cancer. The “fiery” death of the cancer cells actually sets off a chain reaction that makes nearby fibroblasts more protective of the cancer. In other words, chemotherapy meant to destroy the cancer might be fueling its comeback.
The research team, led by Dr. Gao and Dr. Keith Syson Chan, tested this theory using mouse models and samples from human patients. They discovered that a drug called belnacasan can block the harmful inflammatory process triggered by pyroptosis. When combined with chemotherapy, belnacasan reduced the production of collagen and helped chemotherapy work more effectively.
This discovery offers hope for improving bladder cancer treatment, especially for patients whose cancers have become resistant to chemotherapy. The researchers are also exploring whether this approach could help treat other types of cancer, like breast cancer, where similar resistance may be at play.
While more research is needed before this combination therapy can be used in hospitals, the findings point to a new way of thinking about cancer treatment—not just targeting cancer cells directly, but also controlling the body’s response to those treatments.
In the future, combining chemotherapy with drugs that prevent harmful side effects like pyroptosis could make treatments more powerful and give patients a better chance of recovery.
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