Li Yuhua, Tang Tianle, Sun Yang, Chen Gui'e, Yuan Xinrong, Cai De
Department of Pharmacy, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong, People's Republic of China.
Department of Pharmacy, The First Naval Force Hospital of Southern Theatre Command, Zhanjiang, 524005, Guangdong, People's Republic of China.
Discov Oncol. 2025 May 22;16(1):865. doi: 10.1007/s12672-025-02509-z.
Chemotherapy, which aims to eradicate tumor cells and enhance patient survival, is a prevalent approach for tumor treatment. Nevertheless, recurrence and drug resistance resulting from consecutive chemotherapy regimens have emerged as significant factors contributing to the high fatality rates among cancer patients. Numerous studies have revealed that chemicals discharged by injured and deceased cells can trigger the host repair program mediated by toll-like receptor-4 (TLR-4), enhancing tumor resistance. TLR-4 is not only expressed in immune cells but also in various malignant tumor cells, especially inflammation-associated tumor cells, and plays a crucial role in tumor formation, development, and chemoresistance. Endogenous ligands are released upon the killing of tumor cells by chemotherapy drugs, binding to and activating TLR-4, subsequently activating downstream NF-κB and other essential molecules, leading to the release of multiple factors associated with tumor proliferation and invasion, creating a microenvironment conducive to local recurrence and metastasis, and promoting tumor progression and drug resistance. This review assessed studies on the resistance of several tumor cells to commonly utilized anticancer treatments induced by TLR-4 to better comprehend the phenomena and mechanism of TLR-4-dependent resistance, as well as to put forward suggestions and insights for overcoming tumor resistance.
化疗旨在根除肿瘤细胞并提高患者生存率，是一种常见的肿瘤治疗方法。然而，连续化疗方案导致的复发和耐药性已成为癌症患者高死亡率的重要因素。大量研究表明，受损和死亡细胞释放的化学物质可触发由Toll样受体4（TLR-4）介导的宿主修复程序，增强肿瘤耐药性。TLR-4不仅在免疫细胞中表达，也在各种恶性肿瘤细胞中表达，尤其是炎症相关肿瘤细胞，并且在肿瘤形成、发展和化疗耐药中起关键作用。化疗药物杀死肿瘤细胞时会释放内源性配体，其与TLR-4结合并激活TLR-4，随后激活下游的核因子κB和其他重要分子，导致多种与肿瘤增殖和侵袭相关的因子释放，形成有利于局部复发和转移的微环境，促进肿瘤进展和耐药。本综述评估了关于几种肿瘤细胞对TLR-4诱导的常用抗癌治疗产生耐药性的研究，以更好地理解TLR-4依赖性耐药的现象和机制，并为克服肿瘤耐药性提出建议和见解。
