Engineering a drug-inducible pyroptosis platform enables precise tumor suppression in colorectal cancer.

ABSTRACT: Colorectal cancer remains a leading cause of cancer-related mortality, with long-term survival rates hindered by chemoresistance and an immunosuppressive tumor microenvironment. Gene-based therapies offer high specificity but are limited by challenges such as off-target effects, inefficient delivery, and systemic toxicity. Here, we report the design and functional validation of a chemically inducible gene circuit that harnesses Gasdermin E (GSDME) to trigger pyroptotic cell death on demand. We substituted its native proteolytic activation motif with a customized protease recognition sequence. By engineering inducible protease variants whose activity is tightly regulated by an orally bioavailable, clinically approved small molecule, we achieved precise temporal control of pyroptosis. In pat

SUBMITTER: Yao X 

PROVIDER: S-EPMC12767178 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature