Ghiglione Noemi, Abbo Damiano, Bushunova Anastasia, Costamagna Andrea, Porporato Paolo Ettore, Martini Miriam
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center (MBC) Guido Tarone, University of Turin, Torino, Italy.
Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center (MBC) Guido Tarone, University of Turin, Torino, Italy.
Mol Metab. 2025 Feb;92:102089. doi: 10.1016/j.molmet.2024.102089. Epub 2024 Dec 28.
Cellular metabolism plays a pivotal role in the development and progression of pancreatic ductal adenocarcinoma (PDAC), with dysregulated metabolic pathways contributing to tumorigenesis and therapeutic resistance. Distinct metabolic heterogeneity in pancreatic cancer significantly impacts patient prognosis, as variations in metabolic profiles influence tumor behavior and treatment responses.
This review explores the intricate interplay between mitochondrial dynamics, mitophagy, and cellular metabolism in PDAC. We discuss the significance of mitophagy dysregulation in PDAC pathogenesis, emphasizing its influence on treatment responses and prognosis. Furthermore, we analyze the impact of mitochondrial dynamics alterations, including fission and fusion processes, on PDAC progression and tumorigenesis.
Targeting mitochondrial metabolism holds promise for advancing PDAC therapeutics. Ongoing clinical trials underscore the therapeutic potential of modulating key regulators of mitochondrial dynamics and mitophagy. Despite inherent challenges, these approaches offer diverse strategies to enhance treatment efficacy and improve patient outcomes.
细胞代谢在胰腺导管腺癌（PDAC）的发生和发展中起关键作用，代谢途径失调会导致肿瘤发生和治疗耐药性。胰腺癌中明显的代谢异质性显著影响患者预后，因为代谢谱的变化会影响肿瘤行为和治疗反应。
本综述探讨了PDAC中线粒体动力学、线粒体自噬和细胞代谢之间的复杂相互作用。我们讨论了线粒体自噬失调在PDAC发病机制中的重要性，强调其对治疗反应和预后的影响。此外，我们分析了线粒体动力学改变（包括裂变和融合过程）对PDAC进展和肿瘤发生的影响。
靶向线粒体代谢有望推动PDAC治疗的进展。正在进行的临床试验强调了调节线粒体动力学和线粒体自噬关键调节因子的治疗潜力。尽管存在固有挑战，但这些方法提供了多种策略来提高治疗效果和改善患者预后。
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