GSDME (Gasdermin E)

Collectively, IMB5023 concurrently disrupts microtubules and inhibits STAT3 pathway. This dual mechanisms of action positions IMB5023 as a promising therapeutic candidate, particularly for resistant malignancies.

By providing a novel, biologically integrated signature, this model offers a refined tool for prognostic assessment that complements conventional clinical parameters. Ultimately, this pyroptosis-based pathomics model could help guide personalized treatment strategies for ccRCC patients in the future.

Notably, the synergistic antitumor activity of CUR combined with PD-1 blockade in CT26 tumors is strictly dependent on the caspase-3/GSDME axis, as the therapeutic benefit was abolished in GSDME-knockout tumors. These findings establish CUR as a safe and effective adjuvant for PD-1/PD-L1 blockade in MSS CRC, particularly in tumors with low GSDME expression.

In conclusion, FOXO3 is a novel transcription factor of GSDME. Restoration/activation of the FOXO3/GSDME axis could be a promising novel strategy for the treatment of MM.

Pyroptosis is a newly defined form of programmed cell death characterized by plasma membrane perforation, release of cellular contents, and a robust inflammatory response, thereby sensitizing tumors to existing anticancer therapies. Furthermore, the combination of SAQ with sorafenib, a first-line therapeutic agent for HCC, exhibited synergistic antitumor activity both in vitro and in the nude mouse model. These findings not only identify SAQ as a novel pyroptosis-inducer, but also clarify the critical role of the OTUD5-JAK1-GSDME axis in resisting pyroptosis, which may further provide experimental evidence and potential new strategies for treating HCC.

Crucially, this lysosomal rupture also suppressed protective autophagy of tumor cells themselves, thereby reinforcing the cascade activation between caspase-3/GSDME-dependent pyroptosis and cGAS-STING signaling pathway. This lysosomal disruption-nanobomb represents a new strategy for advancing GBM immunotherapy.

In tumor-bearing mice, this nanoplatform synergistically enhances cytotoxic T cell infiltration, reverses immune suppression, and effectively inhibits both primary tumor growth and metastatic progression through the activation of systemic antitumor immunity. This work establishes a versatile strategy that unifies NIR-II phototheranostics, mitochondria-targeting pyroptosis, and TAM reprogramming, providing a robust and targeted approach for cancer immunotherapy.

In selected settings, nano-enabled pyroptosis promotes immune cell infiltration and restores responsiveness to PD-1/PD-L1-based immunotherapy, particularly when combined with chemotherapy or radiotherapy. Despite these advances, clinical translation remains constrained by tumor heterogeneity, delivery inefficiency, and the need for stringent control of inflammatory spillover in lung tissue.

Baohuoside I is a new pyroptosis inducer in LUAD, and combined treatment with Baohuoside I and cisplatin has a synergistic inhibitory effect on LUAD.

Mechanistic studies reveal that 3N-DPQ-COF accumulates efficiently in resistant tumor cells and suppresses cancer stemness in 4T1 and CT26 models, outperforming doxorubicin...Remarkably, even without checkpoint blockade, 3N-DPQ-COF suppresses metastasis and recurrence in chemoresistant 4T1 tumors, achieving >90% tumor inhibition and cure rates exceeding 80%. This study highlights the potential of AIEgen-based COF nanomedicines for overcoming chemoresistance through concurrent modulation of tumor stemness, pyroptosis, and immune activation.