Wang Jiwei, Su Huiling, Wang Min, Ward Richard, An Su, Xu Tian-Rui
State Key Laboratory of Primate Biomedical Research, Kunming University of Science and Technology, Kunming, China.
Center for Pharmaceutical Sciences and Engineering, Kunming University of Science and Technology, Kunming, China.
Med Res Rev. 2025 Jan;45(1):5-28. doi: 10.1002/med.22071. Epub 2024 Aug 12.
Pyroptosis, a newly characterized type of inflammatory programmed cell death (PCD), is usually triggered by multiple inflammasomes which can recognize different danger or damage-associated molecular patterns (DAMPs), leading to the activation of caspase-1 and the cleavage of gasdermin D (GSDMD). Gasdermin family pore-forming proteins are the executers of pyroptosis and are normally maintained in an inactive state through auto-inhibition. Upon caspases mediated cleavage of gasdermins, the pro-pyroptotic N-terminal fragment is released from the auto-inhibition of C-terminal fragment and oligomerizes, forming pores in the plasma membrane. This results in the secretion of interleukin (IL)-1β, IL-18, and high-mobility group box 1 (HMGB1), generating osmotic swelling and lysis. Current therapeutic approaches including chemotherapy, radiotherapy, molecularly targeted therapy and immunotherapy for lung cancer treatment efficiently force the cancer cells to undergo pyroptosis, which then generates local and systemic antitumor immunity. Thus, pyroptosis is recognized as a new therapeutic regimen for the treatment of lung cancer. In this review, we briefly describe the signaling pathways involved in pyroptosis, and endeavor to discuss the antitumor effects of pyroptosis and its potential application in lung cancer therapy, focusing on the contribution of pyroptosis to microenvironmental reprogramming and evocation of antitumor immune response.
细胞焦亡是一种新发现的炎症性程序性细胞死亡（PCD）类型，通常由多种炎性小体触发，这些炎性小体可识别不同的危险或损伤相关分子模式（DAMPs），导致半胱天冬酶-1激活和gasdermin D（GSDMD）裂解。Gasdermin家族成孔蛋白是细胞焦亡的执行者，通常通过自身抑制保持无活性状态。在半胱天冬酶介导的gasdermin裂解后，促细胞焦亡的N端片段从C端片段的自身抑制中释放出来并寡聚化，在质膜上形成孔。这导致白细胞介素（IL）-1β、IL-18和高迁移率族蛋白B1（HMGB1）分泌，引起渗透性肿胀和细胞裂解。目前用于肺癌治疗的化疗、放疗、分子靶向治疗和免疫治疗等方法能有效地促使癌细胞发生细胞焦亡，进而产生局部和全身抗肿瘤免疫。因此，细胞焦亡被认为是一种治疗肺癌的新治疗方案。在本综述中，我们简要描述了细胞焦亡涉及的信号通路，并试图讨论细胞焦亡的抗肿瘤作用及其在肺癌治疗中的潜在应用，重点关注细胞焦亡对微环境重编程和抗肿瘤免疫反应激发的贡献。
