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We show that PFKFB3, an essential regulator of glycolytic metabolism, is significantly upregulated in PCa tissues and CRPC cell lines, where it plays a pivotal role in driving CRPC progression. Knockdown of PFKFB3 or inhibition by a small molecule inhibitor significantly inhibits the growth and invasion of CRPC cells, whereas overexpression promotes malignant behaviors. Mechanistically, PFKFB3 modulates the PI3K\/Akt-Wnt\/\u03b2-catenin pathway, resulting in enhanced tumor cell proliferation. Additionally, combining a PFKFB3 inhibitor with docetaxel produces synergistic anti-CRPC effects and reduces toxicity. 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The study involving six-week-old male BALB\/c nude mice (18\u201320\u2009\u00d7\u2009\n                      g\n                      ) was conducted in accordance with ethical standards for the use and care of animals. Human PCa and BPH tissue samples used in this study were provided by Zhejiang Provincial People\u2019s Hospital. The Zhejiang Provincial People\u2019s Hospital Ethics Committee approved the study (Approval No. KY2024124).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"760"}}