Wu Xiuzhu, Que Haiying, Li Qingfang, Wei Xiawei
Department of Biotherapy, National Clinical Research Center for Geriatric, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, People's Republic of China.
Mol Cancer. 2025 Jun 10;24(1):171. doi: 10.1186/s12943-025-02363-1.
The Wnt/β-catenin signaling pathway is a highly conserved signaling pathway closely linked to cancer development through various biological processes, including oncogenic transformation, genomic instability, cancer cell proliferation, stemness, metabolism, cell death, immune regulation, and metastasis. Notably, its activation plays a crucial role in drug resistance to chemotherapy, targeted therapy and immunotherapy. Recent advances in drug development have identified several targeted inhibitors acting at key nodal points of this pathway, with some demonstrating synergistic efficacy when combined with immunotherapeutic agents. This review provides a comprehensive analysis of current understanding regarding the Wnt/β-catenin pathway in malignancy, emphasizing its multifaceted roles in tumor initiation, therapeutic resistance, and immune regulation. Additionally, we summarized the clinical performance of combination therapies targeting the Wnt/β-catenin pathway in conjunction with chemotherapy, targeted therapy, and immunotherapy. Although clinical development remains at a relatively early stage, pharmacological modulation of Wnt/β-catenin signaling offers considerable potential as a novel therapeutic paradigm in precision oncology.
Wnt/β-连环蛋白信号通路是一条高度保守的信号通路，通过各种生物学过程与癌症发展密切相关，这些过程包括致癌转化、基因组不稳定、癌细胞增殖、干性、代谢、细胞死亡、免疫调节和转移。值得注意的是，其激活在化疗、靶向治疗和免疫治疗的耐药性中起着关键作用。药物开发的最新进展已经确定了几种作用于该通路关键节点的靶向抑制剂，其中一些与免疫治疗药物联合使用时显示出协同疗效。本综述全面分析了目前对恶性肿瘤中Wnt/β-连环蛋白通路的理解，强调了其在肿瘤发生、治疗耐药性和免疫调节中的多方面作用。此外，我们总结了靶向Wnt/β-连环蛋白通路联合化疗、靶向治疗和免疫治疗的联合疗法的临床疗效。尽管临床开发仍处于相对早期阶段，但Wnt/β-连环蛋白信号的药理学调节作为精准肿瘤学中的一种新型治疗模式具有相当大的潜力。
