Autophagy-driven regulation of cisplatin response in human cancers: Exploring molecular and cell death dynamics

作者：Yang Yang, Lixia Liu, Yu Tian, Miaomiao Gu, Yanan Wang, Yanan Wang, Milad Ashrafizadeh, Amir Reza Aref, Israel Cañadas, Daniel J. Klionsky, Arul Goel, Rüssel J. Reiter, Yuzhuo Wang, Yuzhuo Wang, Murtaza M. Tambuwala, Jianyong Zou · 发表于：Cancer Letters · 年份：2024 · DOI：10.1016/j.canlet.2024.216659 · 被引用次数：111 · 研究领域：Autophagy in Disease and Therapy、MicroRNA in disease regulation、Cancer-related molecular mechanisms research

Despite the challenges posed by drug resistance and side effects, chemotherapy remains a pivotal strategy in cancer treatment. A key issue in this context is macroautophagy (commonly known as autophagy), a dysregulated cell death mechanism often observed during chemotherapy. Autophagy plays a cytoprotective role by maintaining cellular homeostasis and recycling organelles, and emerging evidence points to its significant role in promoting cancer progression. Cisplatin, a DNA-intercalating agent known for inducing cell death and cell cycle arrest, often encounters resistance in chemotherapy treatments. Recent studies have shown that autophagy can contribute to cisplatin resistance or insensitivity in tumor cells through various mechanisms. This resistance can be mediated by protective autophagy, which suppresses apoptosis. Additionally, autophagy-related changes in tumor cell metastasis, particularly the induction of Epithelial-Mesenchymal Transition (EMT), can also lead to cisplatin resistance. Nevertheless, pharmacological strategies targeting the regulation of autophagy and apoptosis offer promising avenues to enhance cisplatin sensitivity in cancer therapy. Notably, numerous non-coding RNAs have been identified as regulators of autophagy in the context of cisplatin chemotherapy. Thus, therapeutic targeting of autophagy or its associated pathways holds potential for restoring cisplatin sensitivity, highlighting an important direction for future clinical research.