Balance Cell Apoptosis and Pyroptosis of Caspase-3-Activating Chemotherapy for Better Antitumor Therapy

上睑下垂 程序性细胞死亡 细胞凋亡 化疗 癌症研究 医学 半胱氨酸蛋白酶 细胞 药理学 化学 内科学 生物化学
作者
Ling‐Jiao Li,Shengmei Wang,Wenhu Zhou
出处
期刊:Cancers [MDPI AG]
卷期号:15 (1): 26-26 被引量:59
标识
DOI:10.3390/cancers15010026
摘要

Chemotherapy is a standard treatment modality in clinic that exerts an antitumor effect via the activation of the caspase-3 pathway, inducing cell death. While a number of chemotherapeutic drugs have been developed to combat various types of tumors, severe side effects have been their common limitation, due to the nonspecific drug biodistribution, bringing significant pain to cancer patients. Recently, scientists found that, besides apoptosis, chemotherapy could also cause cell pyroptosis, both of which have great influence on the therapeutic index. For example, cell apoptosis is, generally, regarded as the main mechanism of killing tumor cells, while cell pyroptosis in tumors promotes treatment efficacy, but in normal tissue results in toxicity. Therefore, significant research efforts have been paid to exploring the rational modulation mode of cell death induced by chemotherapy. This critical review aims to summarize recent progress in the field, focusing on how to balance cell apoptosis and pyroptosis for better tumor chemotherapy. We first reviewed the mechanisms of chemotherapy-induced cell apoptosis and pyroptosis, in which the activated caspase-3 is the key signaling molecule for regulating both types of cell deaths. Then, we systematically discussed the rationale and methods of switching apoptosis to pyroptosis for enhanced antitumor efficacy, as well as the blockage of pyroptosis to decrease side effects. To balance cell pyroptosis in tumor and normal tissues, the level of GSDME expression and tumor-targeting drug delivery are two important factors. Finally, we proposed potential future research directions, which may provide guidance for researchers in the field.

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