Cysteinyl
aspartate specific
proteinase (Caspase)-8 has long been considered a promoter of apoptosis and part of the mechanism by which cytotoxic drugs kill
cancer cells. With the continuous exploration of the types of programmed cell death, an increasing number of studies have confirmed that
caspase-8 plays an important role in
cancer. Recently, scholars have proposed the term "PANoptosis," which mainly includes three programmed cell death modes, namely pyroptosis, apoptosis and necroptosis. In addition to mediating endogenous apoptotic pathways,
caspase-8 can also participate in the cleavage of gasdermin (GSDM) family
proteins to induce pyroptosis. Furthermore, the expression of enzymatically inactive
caspase-8 (C362S) can cause embryonic lethality and inflammatory tissue destruction in mice by inducing necroptosis and pyroptosis. Therefore, the activation and deletion of
caspase-8 enzyme activity, as well as the knockout of the coding gene, are closely related to "PANoptosis." In addition,
caspase-8 can also improve the tumor microenvironment and enhance
tumor antiimmunity. Studies have shown that
caspase-8 is also associated with
tumor growth and invasion, angiogenesis and
metastasis, therapeutic resistance and poor clinical outcomes. Therefore, it is very important to measure the
cancer-promoting and anticancer effects of
caspase-8 and find a balance, and to study its role in the effect of "PANoptosis" in depth. This article reviews the role of
caspase-8 in "PANoptosis" in
cancer to provide new strategies and targets for
cancer.