Beyond symptomatic relief for chemotherapy-induced peripheral neuropathy: Targeting the source

Area of Science:

• Oncology
• Neuroscience
• Pharmacology

Background:

• Chemotherapy-induced peripheral neuropathy (CIPN) is a common and persistent side effect of cancer treatment, impacting over 60% of patients.
• Current treatments for CIPN primarily offer symptomatic relief and lack significant efficacy.
• There is a critical need for mechanism-based interventions that modify CIPN without compromising chemotherapy's antitumor effects.

Purpose of the Study:

• To explore the role of neuronal mitochondrial dysfunction and nitro-oxidative stress in CIPN etiology.
• To review novel therapeutic strategies targeting these pathways for CIPN prevention or reversal.
• To bridge the gap between preclinical research and clinical application for CIPN management.

Main Methods:

• Review of existing literature on CIPN mechanisms and potential therapeutic targets.
• Discussion of the role of mitochondria in cellular energy production and apoptosis.
• Analysis of novel drug candidates including mitochondrial protectants, HDAC6 inhibitors, metformin, antioxidants, and anti-inflammatory agents.

Main Results:

• Neuronal mitochondrial dysfunction and nitro-oxidative stress are identified as key pathways in CIPN.
• Several novel drug classes show potential for protecting mitochondria and inhibiting oxidative stress.
• These include pifithrin-μ, HDAC6 inhibitors, metformin, antioxidants, peroxynitrite decomposition catalysts, and IL-10.

Conclusions:

• Targeting mitochondrial pathways and nitro-oxidative stress offers a promising approach for managing CIPN.
• Developing mechanism-based therapies is essential for effective CIPN treatment.
• Further research is needed to translate these findings into clinical practice for cancer survivors.