Epigenetic regulation of pyroptosis in cancer: Molecular pathogenesis and targeting strategies

Immune checkpoint blockade therapy has revolutionized the field of cancer treatment, leading to durable responses in patients with advanced and metastatic cancers where conventional therapies were insufficient. However, factors like immunosuppressive cells and immune checkpoint molecules within the tumor microenvironment (TME) can suppress the immune system and thus negatively affect the efficiency of immune checkpoint inhibitors. Pyroptosis, a gasdermin-induced programmed cell death, could transform “cold tumors” to “hot tumors” to improve the milieu of TME, thus enhancing the immune response and preventing tumor growth. Recently, evidence showed that epigenetics could regulate pyroptosis, which further affects tumorigenesis, suggesting that epigenetics-based tumor cells pyroptosis could be a promising therapeutic strategy. Hence, this review focuses on the pyroptotic mechanism and summarizes three common types of epigenetics, DNA methylation, histone modification, and non-coding RNA, all of which have a role in regulating the expression of transcription factors and proteins involved in pyroptosis in cancer. Especially, we discuss targeting strategies on epigenetic-regulated pyroptosis and provide insights on the future trend of cancer research which may fuel cancer therapies into a new step.