Cao Zi-Tong, Mao Jia-Luo, Huang Chang-Ying, Wang Han-Lin, Wang Ming-Zhi, Wang Wen-Long, Zhou Yu-Bo, Li Jia
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China.
National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Acta Pharmacol Sin. 2025 May 8. doi: 10.1038/s41401-025-01563-1.
PRL-3, a protein tyrosine phosphatase (PTP), has a significant influence on the pathogenesis of various cancers with its overexpression significantly correlating with tumor invasion, metastasis and poor prognosis. It significantly affects tumor cell behavior through its involvement in cell proliferation, migration and metabolic processes. Furthermore, the interaction between PRL-3 and the tumor microenvironment characterized by its adaptability to stress and its role in metabolic reprogramming enhances tumor cell survival and dissemination. Targeted therapies against PRL-3, encompassing small molecule inhibitors and the monoclonal antibody PRL-3-zumab, have shown promise in clinical and preclinical studies, presenting new avenues for cancer treatment. In addition, innovative approaches such as CAAX motif-targeting agents and PRL-3 degradation strategies hold promise for developing more precise and effective interventions. This review explores PRL-3's multifaceted roles across different tumor types and microenvironments, while discussing current and emerging therapeutic strategies aimed at exploiting its oncogenic potential.
PRL-3是一种蛋白质酪氨酸磷酸酶(PTP),对多种癌症的发病机制有重大影响,其过表达与肿瘤侵袭、转移及不良预后显著相关。它通过参与细胞增殖、迁移和代谢过程,显著影响肿瘤细胞行为。此外,PRL-3与肿瘤微环境之间的相互作用,其特点是对压力的适应性及其在代谢重编程中的作用,增强了肿瘤细胞的存活和扩散。针对PRL-3的靶向治疗,包括小分子抑制剂和单克隆抗体PRL-3-zumab,在临床和临床前研究中已显示出前景,为癌症治疗提供了新途径。此外,诸如靶向CAAX基序的药物和PRL-3降解策略等创新方法有望开发出更精确有效的干预措施。本综述探讨了PRL-3在不同肿瘤类型和微环境中的多方面作用,同时讨论了旨在利用其致癌潜力的当前和新兴治疗策略。