Cancer is hallmarked by uncontrolled cell proliferation and enhanced cell survival, driven by a complex interplay of factors—including genetic and epigenetic changes—that disrupt metabolic and signaling pathways and impair organelle function. While the roles of mitochondria and the endoplasmic reticulum in cancer are widely recognized, emerging research is now drawing attention to the involvement of peroxisomes in tumor biology. Peroxisomes are essential for lipid metabolism, including fatty acid α- and β-oxidation, the synthesis of docosahexaenoic acid, bile acids, and ether lipids, as well as maintaining redox balance. Despite their critical functions, the role of peroxisomes in oncogenesis remains inadequately explored. Prostate cancer (PCa), the second most common cancer in men worldwide, exhibits a unique metabolic profile compared to other solid tumors. In contrast to the glycolysis-driven Warburg effect, primary PCa relies primarily on lipogenesis and oxidative phosphorylation. Peroxisomes are intricately involved in the metabolic adaptations of PCa, influencing both disease progression and therapy resistance. Key alterations in peroxisomal activity in PCa include the increased oxidation of branched-chain fatty acids, upregulation of α-methylacyl coenzyme A racemase (a prominent PCa biomarker), and downregulation of 1-alkyl-glycerone-3-phosphate synthase and catalase. This review critically examines the role of peroxisomes in PCa metabolism, progression, and therapeutic response, exploring their potential as biomarkers and targets for therapy. We also consider their relationship with androgen receptor signaling. A deeper understanding of peroxisome biology in PCa could pave the way for new therapies to improve patient outcomes.
癌症的特征在于细胞增殖失控和存活能力增强，其驱动因素复杂多样——包括遗传和表观遗传改变——这些因素破坏代谢与信号通路，并损害细胞器功能。虽然线粒体和内质网在癌症中的作用已得到广泛认知，但新兴研究正逐渐揭示过氧化物酶体在肿瘤生物学中的参与。过氧化物酶体对脂质代谢至关重要，包括脂肪酸α-和β-氧化、二十二碳六烯酸、胆汁酸及醚脂的合成，并维持氧化还原平衡。尽管功能关键，过氧化物酶体在肿瘤发生中的作用仍未得到充分探索。前列腺癌作为全球男性第二大常见癌症，相较于其他实体肿瘤展现出独特的代谢特征。与糖酵解驱动的瓦博格效应不同，原发性前列腺癌主要依赖脂肪生成和氧化磷酸化。过氧化物酶体深度参与前列腺癌的代谢适应过程，影响疾病进展和治疗抵抗。前列腺癌中过氧化物酶体活性的关键改变包括支链脂肪酸氧化增强、α-甲基酰基辅酶A消旋酶（前列腺癌重要生物标志物）上调，以及1-烷基-甘油酮-3-磷酸合酶和过氧化氢酶下调。本综述系统探讨过氧化物酶体在前列腺癌代谢、进展及治疗反应中的作用，探索其作为生物标志物和治疗靶点的潜力，并考察其与雄激素受体信号通路的关系。深入理解前列腺癌中过氧化物酶体生物学，可能为开发改善患者预后的新疗法开辟道路。
Peroxisomal Alterations in Prostate Cancer: Metabolic Shifts and Clinical Relevance
肿瘤(癌症)患者之家