Chemotherapeutics Associated Central Nervous System Toxicity: Mechanistic Insights

Background: Over the past two decades, cancer has emerged as a major global health concern, affecting a significant portion of the population. While chemotherapeutic agents have revolutionized cancer treatment, they have also introduced a range of adverse effects, with neurotoxicity being a critical complication that can severely limit treatment options. Objective: This review aims to provide a comprehensive analysis of the mechanisms underlying chemotherapy-induced neurotoxicity and to identify strategies for mitigating its effects. Method: A comprehensive bibliographic investigation was conducted using scientific databases such as PubMed, Scopus, Web of Science, SciELO, NISCAIR, and Google Scholar. The search included peer-reviewed articles published in English up to December 2024, focusing on the neurotoxic effects of chemotherapy on the central nervous system (CNS). Keywords included “chemotherapy,” “neurotoxicity,” “CNS toxicity,” “oxidative stress,” “neuronal apoptosis,” “hippocampus toxicity,” “cortical toxicity,” “CNS syndromes,” and “neuroinflammation.” Inclusion criteria were studies that reported mechanistic insights, clinical observations, and experimental findings on chemotherapyinduced CNS toxicity. Relevant articles were screened based on title and abstract, followed by a fulltext evaluation to extract key data and identify patterns in neurotoxic mechanisms and clinical manifestations. Results: Patients with underlying conditions such as diabetes, hereditary neuropathies, or previous exposure to neurotoxic agents are particularly susceptible to chemotherapy-induced peripheral and central neurotoxicity. Identified mechanisms include microglial activation, neuronal apoptosis, demyelination, and oxidative stress, especially affecting cortical and hippocampal regions. These processes contribute to cognitive and functional impairments that manifest as transient or progressive neurological symptoms, including cognitive deficits, aphasia, hemiparesis, and dementia. Differentiating these effects from cancer progression remains a clinical challenge and may result in diagnostic delays or treatment errors. Conclusion: Establishing a clear mechanistic understanding of chemotherapy-induced neurotoxicity is essential for advancing therapeutic strategies that minimize adverse effects. Enhanced knowledge of underlying biological pathways will support the development of neuroprotective interventions and improve patient management outcomes in oncology settings.