Michetti Federica, Cirone Mara, Strippoli Raffaele, D'Orazi Gabriella, Cordani Marco
Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
Department of Epidemiology, Preclinical Research and Advanced Diagnostics, National Institute for Infectious Diseases L., Spallanzani, IRCCS, Via Portuense, 292, 00149, Rome, Italy.
Discov Oncol. 2025 Apr 23;16(1):592. doi: 10.1007/s12672-025-02400-x.
Pancreatic ductal adenocarcinoma (PDAC) is characterised by early metastasis and resistance to anti-cancer therapy, leading to an overall poor prognosis. Macroautophagy (hereinafter referred to as autophagy) is a conserved cellular homeostasis mechanism that degrades various cargoes (e.g., proteins, organelles, and pathogens) mainly playing a role in promoting survival under environmental stress. Autophagy is an essential defense mechanism against PDAC initiation, acting on multiple levels to maintain cellular and tissue homeostasis. However, autophagy is also intimately involved in the molecular mechanisms driving PDAC progression, facilitating the adaptation of cancer cells to the tumor microenvironment's harsh conditions. In this review, we examine the complex role of autophagy in PDAC and assess the potential of modulating autophagy as a therapeutic strategy. By reviewing current research and clinical trials, we seek to elucidate how targeting autophagy can disrupt PDAC tumor survival mechanisms, enhance the efficacy of existing treatments, and ultimately improve patient outcomes.
胰腺导管腺癌（PDAC）的特征是早期转移和对抗癌治疗耐药，导致总体预后较差。巨自噬（以下简称自噬）是一种保守的细胞稳态机制，可降解各种货物（如蛋白质、细胞器和病原体），主要在环境应激下促进细胞存活中发挥作用。自噬是抵抗PDAC起始的重要防御机制，在多个层面发挥作用以维持细胞和组织稳态。然而，自噬也密切参与驱动PDAC进展的分子机制，促进癌细胞适应肿瘤微环境的恶劣条件。在这篇综述中，我们研究了自噬在PDAC中的复杂作用，并评估了调节自噬作为一种治疗策略的潜力。通过回顾当前的研究和临床试验，我们试图阐明靶向自噬如何破坏PDAC肿瘤存活机制、提高现有治疗的疗效，并最终改善患者预后。
