The role of lysophosphatidic acid metabolism in castration-resistant prostate cancer progression.

Prostate cancer (PCa) is a leading malignancy in men, with mortality primarily attributed to progression to castration-resistant prostate cancer (CRPC). Although androgen deprivation therapy (ADT) initially demonstrates efficacy, most advanced patients eventually develop CRPC-a stage characterized by limited treatment options and poor prognosis. Elucidating the molecular mechanisms underlying CRPC transformation therefore represents a research priority. Tumor metabolic reprogramming has emerged as a hallmark of cancer, and among various metabolic pathways, lysophosphatidic acid (LPA)-a bioactive lipid mediator-has been increasingly implicated in PCa progression, particularly CRPC transformation. This review systematically examines LPA metabolic sources and signal transduction mechanisms and explores how LPA promotes CRPC progression through driving proliferation, survival, invasion, therapy resistance, and tumor microenvironment remodeling. Finally, we discuss the potential and challenges of targeting the LPA signaling pathway as a novel therapeutic strategy for CRPC.