Gu Qingdan, Zou Jiazhen, Zhou Ying, Deng Qiuchan
Department of Clinical Laboratory, Shenzhen Longhua District Central Hospital, Guangdong Medical University, Shenzhen, Guangdong, China.
Department of Laboratory Medicine, Shenzhen Second People's Hospital, The First Affiliated 5 Hospital of Shenzhen University, Health Science Center, Shenzhen, China.
Front Oncol. 2023 Mar 20;13:1133013. doi: 10.3389/fonc.2023.1133013. eCollection 2023.
Inflammasomes, composed of the nucleotide-binding oligomerization domain(NOD)-like receptors (NLRs), are immune-functional protein multimers that are closely linked to the host defense mechanism. When NLRs sense pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), they assemble into inflammasomes. Inflammasomes can activate various inflammatory signaling pathways, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, and produce a large number of proinflammatory cytokines, which are closely associated with multiple cancers. They can also accelerate the occurrence and development of cancer by providing suitable tumor microenvironments, promoting tumor cell proliferation, and inhibiting tumor cell apoptosis. Therefore, the exploitation of novel targeted drugs against various inflammasomes and proinflammatory cytokines is a new idea for the treatment of cancer. In recent years, more than 50 natural extracts and synthetic small molecule targeted drugs have been reported to be in the research stage or have been applied to the clinic. Herein, we will overview the mechanisms of inflammasomes in common cancers and discuss the therapeutic prospects of natural extracts and synthetic targeted agents.
炎症小体由核苷酸结合寡聚化结构域(NOD)样受体(NLR)组成,是与宿主防御机制密切相关的具有免疫功能的蛋白质多聚体。当NLR感知病原体相关分子模式(PAMP)和损伤相关分子模式(DAMP)时,它们会组装成炎症小体。炎症小体可激活多种炎症信号通路,包括核因子κB(NF-κB)和丝裂原活化蛋白激酶(MAPK)信号通路,并产生大量促炎细胞因子,这些细胞因子与多种癌症密切相关。它们还可通过提供合适的肿瘤微环境、促进肿瘤细胞增殖和抑制肿瘤细胞凋亡来加速癌症的发生和发展。因此,开发针对各种炎症小体和促炎细胞因子的新型靶向药物是治疗癌症的新思路。近年来,已有50多种天然提取物和合成小分子靶向药物报道处于研究阶段或已应用于临床。在此,我们将概述炎症小体在常见癌症中的作用机制,并讨论天然提取物和合成靶向药物的治疗前景。