Zhao Xi, Ma Yunong, Luo Jiayang, Xu Kexin, Tian Peilin, Lu Cuixia, Song Jiaxing
Medical Scientific Research Center, Life Sciences Institute, Guangxi Medical University, Nanning, 530021, China.
China Medical College of Guangxi University, Guangxi University, Nanning, 530004, China.
Heliyon. 2024 Aug 12;10(16):e35989. doi: 10.1016/j.heliyon.2024.e35989. eCollection 2024 Aug 30.
The WNT/β-catenin signaling pathway plays crucial roles in tumorigenesis and relapse, metastasis, drug resistance, and tumor stemness maintenance. In most tumors, the WNT/β-catenin signaling pathway is often aberrantly activated. The therapeutic usefulness of inhibition of WNT/β-catenin signaling has been reported to improve the efficiency of different cancer treatments and this inhibition of signaling has been carried out using different methods including pharmacological agents, short interfering RNA (siRNA), and antibodies. Here, we review the WNT-inhibitory effects of some FDA-approved drugs and natural products in cancer treatment and focus on recent progress of the WNT signaling inhibitors in improving the efficiency of chemotherapy, immunotherapy, gene therapy, and physical therapy. We also classified these FDA-approved drugs and natural products according to their structure and physicochemical properties, and introduced briefly their potential mechanisms of inhibiting the WNT signaling pathway. The review provides a comprehensive understanding of inhibitors of WNT/β-catenin pathway in various cancer therapeutics. This will benefit novel WNT inhibitor development and optimal clinical use of WNT signaling-related drugs in synergistic cancer therapy.
WNT/β-连环蛋白信号通路在肿瘤发生、复发、转移、耐药性及肿瘤干性维持中发挥着关键作用。在大多数肿瘤中，WNT/β-连环蛋白信号通路常常异常激活。据报道，抑制WNT/β-连环蛋白信号通路具有治疗作用，可提高不同癌症治疗的效率，并且已通过包括药理学试剂、小干扰RNA（siRNA）和抗体在内的不同方法来实现这种信号通路的抑制。在此，我们综述了一些美国食品药品监督管理局（FDA）批准的药物和天然产物在癌症治疗中的WNT抑制作用，并聚焦于WNT信号通路抑制剂在提高化疗、免疫治疗、基因治疗及物理治疗效率方面的最新进展。我们还根据这些FDA批准的药物和天然产物的结构和理化性质对其进行了分类，并简要介绍了它们抑制WNT信号通路的潜在机制。该综述提供了对WNT/β-连环蛋白通路抑制剂在各种癌症治疗中的全面理解。这将有助于新型WNT抑制剂的开发以及WNT信号相关药物在协同癌症治疗中的最佳临床应用。
