Dual regulation of PINK1/PARKIN-mediated mitochondrial autophagy in ovarian cancer progression and drug resistance: mechanisms and therapeutic potentials

Ovarian cancer (OC) is a common primary female malignancy globally.It is characterized by a high rate of confirmed diagnosis at an advanced stage (around 70%), abdominal and distant metastases at initial diagnosis, and relatively lower average 5-year survival rate worldwide (< 30%).This undoubtedly greatly increases the difficulty and complexity of the treatment.The therapeutic effect of OC is primarily compromised by the mechanism of chemotherapy resistance, which is complex and has not been fully elucidated.Beyond producing negative impact on the effectiveness of existing treatment strategies, the resistance of cancer cells to chemotherapeutic agents may also prompt the medical community to constantly explore new treatment approaches.Therefore, in order to develop more effective treatment plans, it highlights the importance and necessity of achieving a thorough understanding of the pathogenesis of OC and the mechanism of chemotherapy resistance.Currently, mitophagy, an intracellular self-degradation process, has been documented to be pivotal in the development of OC and in chemotherapy resistance.It functions to maintain the stability of the intracellular environment through the autophagy mechanism, regulate cellular energy metabolism, and participate in immune responses, supporting its potential of inhibiting tumor growth theoretically.In particular, the PINK1/PARKIN pathway demonstrates a unique bidirectional regulatory effect in tumor growth regulation and chemotherapy resistance reversal.Its dynamic regulatory mechanism in platinum-based resistance of OC has revealed potential therapeutic targets.Accordingly, with emphasis on the bidirectional regulatory role of the PINK1/PARKIN signaling pathway-mediated mitophagy in inhibiting the growth of OC and reversing chemotherapy resistance, this study aimed to integrate the latest research results, and provide innovative treatment strategies and ideas for OC treatment and chemotherapy efficacy optimization.