review · Molecular and Cellular Biochemistry
Cyclophosphamide significantly improves survival for cancer patients, but its clinical utility is constrained by neurotoxic side effects. These neurological complications manifest as cognitive impairment, anxiety, depression, and motor dysfunction. Research indicates that the underlying molecular drivers of this damage include oxidative brain injury, neuroinflammation, apoptotic neuronal cell death, and disturbances in neurotransmitters and neurotrophic factors. Although numerous protective substances show promise in animal models, none have advanced to human clinical trials, leaving a lack of clinical evidence supporting their use. Furthermore, research has not yet evaluated whether these experimental neuroprotective candidates interfere with the anticancer efficacy of cyclophosphamide in tumour-bearing subjects. Dedicated clinical trials and tumour interaction studies are required to determine whether these strategies can safely protect neurological function during chemotherapy.
Cyclophosphamide is an essential chemotherapy drug, yet its neurological side effects diminish quality of life and restrict therapeutic dosing. Understanding the molecular pathways behind brain toxicity helps researchers pinpoint interventions that safeguard neurological health, potentially enabling cancer patients to receive effective chemotherapy regimens with fewer debilitating cognitive and psychological complications.
The identified biological targets could inform the development of adjuvant neuroprotective drugs for oncology patients. This research is relevant to pharmaceutical developers and clinical researchers seeking supportive cancer therapies. However, practical application remains at an early preclinical stage, as prospective neuroprotective agents must first be tested for non-interference with chemotherapy in tumour models before advancing to human clinical trials.
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Cyclophosphamide has drastically enhanced the expectancy and quality of life of cancer patients. However, it is accompanied by diverse neurological complications which are considered a dose-limiting adverse effect. Neurotoxicity caused by cyclophosphamide can manifest in numerous manners including anxiety, depression, motor dysfunction and cognitive deficits. This review article offers an overview on cyclophosphamide-induced neurotoxicity, providing a unified point of view on the possible underlying molecular mechanisms including oxidative brain damage, neuroinflammation, apoptotic neuronal cell death as well as disruption of the balance of brain neurotransmitters and neurotrophic factors. Besides, this review sheds light on the promising protective agents that have been investigated using preclinical animal models as well as their biological targets and protection mechanisms. Despite promising results in experimental models, none of these agents has been studied in clinical trials. Thus, there is lack of evidence to advocate the use of any neuroprotective agent in the clinical setting. Furthermore, none of the protective agents has been evaluated for its effect on the anticancer activity of cyclophosphamide in tumor-bearing animals. Therefore, there is a great necessity for adequate well-designed clinical studies for evaluation of the therapeutic values of these candidates. Conclusively, this review summarizes the molecular mechanisms accounting for cyclophosphamide-induced neurotoxicity together with the potential protective strategies seeking for downgrading this neurological complication, thus enhancing the quality of life and well-being of cancer patients treated with cyclophosphamide.
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DOI: 10.1007/s11010-023-04805-0
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