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

Yang Yang, Lixia Liu, Yu Tian, Miaomiao Gu, Yanan Wang, Milad Ashrafizadeh, Amir Reza Aref, Israel Cañadas, Daniel J Klionsky, Arul Goel, Russel J Reiter, Yuzhuo Wang, Murtaza Tambuwala, Jianyong Zou

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish
Article number216659
Pages (from-to)216659
JournalCancer Letters
Volume587
Early online dateFeb 15 2024
DOIs
StatePublished - Apr 10 2024

Keywords

  • Apoptosis
  • Autophagy
  • Cancer chemotherapy
  • Cisplatin
  • Drug resistance
  • Antineoplastic Agents/pharmacology
  • Cisplatin/pharmacology
  • Humans
  • Cell Line, Tumor
  • Neoplasms/drug therapy
  • Drug Resistance, Neoplasm

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