Chemotherapy and the pediatric brain

Area of Science:

• Pediatric Oncology
• Neuroscience
• Cancer Therapeutics

Background:

• Childhood cancer survival rates are increasing, highlighting the need to address long-term neurocognitive and psychiatric outcomes.
• Neurobehavioral morbidity, including cognitive deficits and emotional health issues, significantly impacts the quality of life for childhood cancer survivors.
• Chemotherapy-induced central nervous system (CNS) toxicity is a major contributor to neurobehavioral issues in these survivors.

Purpose of the Study:

• To review key publications on chemotherapy neurotoxicity in pediatric cancers.
• To summarize the potential underlying pathomechanisms of chemotherapy-induced brain injury in children.
• To inform clinical practice and future research regarding neuroprotection strategies.

Main Methods:

• Literature review of clinical and preclinical studies.
• Analysis of studies investigating chemotherapy effects on the pediatric central nervous system (CNS).
• Examination of mechanisms including excitotoxicity, apoptosis, DNA damage, oxidative stress, telomere shortening, and impaired neurogenesis.

Main Results:

• Clinical studies link chemotherapy to leukoencephalopathies and reduced grey/white matter volumes, correlating with neurocognitive deficits.
• Preclinical research demonstrates chemotherapy drugs are neurotoxic, causing brain injury via excitotoxic and apoptotic pathways.
• Chemotherapy impacts developing brains by affecting myelination, synaptogenesis, neurogenesis, and neuronal network formation.

Conclusions:

• Chemotherapy poses significant risks to neurodevelopment in children undergoing cancer treatment.
• Understanding the molecular and cellular mechanisms of neurotoxicity is essential for mitigating long-term effects.
• Further research is needed to develop strategies for neuroprotection in pediatric cancer patients.