Pathogenesis of platinum-induced peripheral neurotoxicity: Insights from preclinical studies

Area of Science:

• Neuroscience
• Pharmacology
• Oncology

Background:

• Platinum-based chemotherapy drugs can cause dose-limiting sensory peripheral neurotoxicity (PIPN), significantly reducing patient quality of life.
• Currently, no effective treatments exist for PIPN; management relies on reducing chemotherapy dosage or cessation.
• Preclinical research has extensively studied PIPN, developing various in vitro and in vivo models to understand its mechanisms.

Purpose of the Study:

• To review and critically analyze the pathogenic mechanisms underlying platinum-induced peripheral neurotoxicity (PIPN).
• To explore the molecular pathways, including apoptosis and oxidative stress, involved in PIPN development.
• To assess the utility and limitations of current preclinical models in elucidating PIPN pathogenesis.

Main Methods:

• Comprehensive literature review of preclinical research on PIPN.
• Critical analysis of in vitro and in vivo models used to study PIPN.
• Examination of molecular mechanisms, including DNA platination, oxidative stress, and apoptosis in dorsal root ganglion (DRG) sensory neurons.

Main Results:

• Apoptosis of peripheral neurons, particularly DRG sensory neurons, is a key mechanism in PIPN.
• PIPN pathogenesis involves nuclear and mitochondrial DNA platination and increased oxidative stress due to depleted antioxidant defenses.
• Despite extensive research, a gap remains between preclinical findings and clinical therapeutic applications.

Conclusions:

• Understanding the complex molecular mechanisms of PIPN is crucial for developing effective neuroprotective strategies.
• Further research is needed to bridge the gap between preclinical models and clinical translation for PIPN treatment.
• Elucidating remaining pathogenic mechanisms of PIPN is essential for improving chemotherapy safety and patient outcomes.