Apoptosis has long been recognized as a mechanism that kills the cancer cells by cytotoxic drugs. In recent years, studies have proved that pyroptosis can also shrink tumors and inhibit cells proliferation. Both apoptosis and pyroptosis are caspase-dependent programmed cell death pathways. Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death. When GSDME is highly expressed, the active caspase-3 cuts it and releases the N-terminal domain to punch holes in the cell membrane, resulting in cell swelling, rupture, and death. When the expression of GSDME is low, it will lead to the classical mechanism of tumor cell death, which is apoptosis. More interestingly, researchers have found that GSDME can also be located upstream of caspase-3, connecting extrinsic, and intrinsic apoptotic pathways. Then, promoting caspase-3 activation, and forming a self-amplifying feed-forward loop. GSDME-mediated pyroptosis is correlated with the side effects of chemotherapy and anti-tumor immunity. This article mainly reviews the caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer, to provide new strategies and targets for cancer treatment.

Environmental factors and genetic mutation have caused cancer incidence and mortality to rapidly increase. Cancer has become one of the crucial causes of death worldwide, and is becoming a major public health problem. 1 The traditional core types of cancer treatment are surgery, chemo-therapy, and radiation therapy, which can reduce tumor cell proliferation by inducing cancer cell death. 2 However, accumulating evidence has shown that tumors often relapse and it has been suggested that successful oncotherapy requires prolonged antineoplastic immunity. 3 The field of cancer immunotherapy (CIT) has emerged in recent years and aims to stimulate the body's immune system to create a robust immune response that can kill cancer cells. 4 This type of treatment can induce immunogenic cell death in different ways and achieve long-term anticancer immunity. 5 Although the application of CIT has been considered for a broad range of tumors, only a minority of patients achieve a satisfactory treatment effect due to immune escape. These results indicate that the immune system is intricate and still not well managed. 6 Thus, it is necessary to explore the mechanisms involved in CIT to develop more efficient methods of treatment for better cancer prevention and treatment.

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.

Chemotherapy has been a conventional paradigm for cancer treatment, and multifarious chemotherapeutic drugs have been widely employed for decades with significant performances in suppressing tumors. Moreover, some of the antitumor...

Cancer has been a serious health hazard to the people all over the world with its high incidence and horrible mortality. In recent years, tumor vaccines in immunotherapy have become a hotspot in cancer therapy due to their many practical advantages and good therapeutic potentials. Among the various vaccines, nanovaccine utilized nanoparticles (NPs) as the carrier and/or adjuvant has presented significant therapeutic effect in cancer treatment. For tumor nanovaccines, unmethylated cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN) is a commonly used adjuvant. It has been reported that CpG ODN was the most effective immune stimulant among the currently known adjuvants. It could be recognized by toll-like receptor 9 (TLR9) to activate humoral and cellular immunity for preventing or treating cancer. In this review, the topic of CpG-based nanovaccines for cancer immunotherapy will be focused. The types and properties of different CpG will be introduced in detail first, and then some representative tumor nanovaccines will be reviewed according to the diverse loading modes of CpG, such as electrostatic adsorption, covalent bonding, hydrophilic and hydrophobic interaction, and DNA self-assembly, for summarizing the current progress of CpG-based tumor nanovaccines. Finally, the challenges and future perspectives will be discussed. It is hoped that this review will provide valuable references for the development of nanovaccines in cancer immunotherapy.