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PRL-3: unveiling a new horizon in cancer therapy

Acta Pharmacologica Sinica volume 46, pages 2597–2607 (2025)Cite this article

Abstract

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.

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Fig. 1
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Fig. 4: The structure of PRL-3 and the predicted binding pockets of PRL-3 inhibitors by AlphaFold 3.
Fig. 5

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Acknowledgements

This work was supported by Shanghai Science and Technology Development Funds (24YF2755300), Guangdong High-level New R&D Institute (2019B090904008), and Guangdong High-level Innovative Research Institute (2021B0909050003). Additionally, we are grateful for the insightful exchanges with our lab colleagues.

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  1. These authors contributed equally: Zi-tong Cao, Jia-luo Mao

Authors and Affiliations

  1. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, 210009, China

    Zi-tong Cao & Jia Li

  2. National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China

    Zi-tong Cao, Jia-luo Mao, Chang-ying Huang, Han-lin Wang, Yu-bo Zhou & Jia Li

  3. Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan, 528400, China

    Zi-tong Cao, Jia-luo Mao, Ming-zhi Wang, Yu-bo Zhou & Jia Li

  4. School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, 210023, China

    Jia-luo Mao, Ming-zhi Wang, Yu-bo Zhou & Jia Li

  5. State Key Laboratory of Chemical Biology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China

    Chang-ying Huang, Han-lin Wang & Jia Li

  6. University of Chinese Academy of Sciences, Beijing, 100049, China

    Chang-ying Huang & Jia Li

  7. School of Pharmaceutical Science, Jiangnan University, Wuxi, 214122, China

    Wen-long Wang

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Cao, Zt., Mao, Jl., Huang, Cy. et al. PRL-3: unveiling a new horizon in cancer therapy. Acta Pharmacol Sin 46, 2597–2607 (2025). https://doi.org/10.1038/s41401-025-01563-1

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