Document Type : Original Article
Authors
1
Department of Molecular Biology, Molecular Biology Research & Studies Institute, Assiut University, 71516 Assiut - Egypt.
2
Department of Zoology and Entomology, Faculty of Science, Assiut University, 71516Assiut, Egypt Department of Basic Science, School of Biotechnology, Badr University in Assiut, Egypt
3
Department of Pathology and Clinical Pathology, School of Veterinary Medicine, Badr University in Assiut, Egypt & Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, Assiut University,71516 Assiut Egypt Department of Pathology and Clinical Pathology, School of Veterinary Medicine, Badr University in Assiut, Egypt
Abstract
Vincristine sulfate (VCR), a vinca alkaloid derived from Catharanthus roseus, has been a cornerstone in cancer therapy since its FDA approval in the 1960s. Despite its efficacy in treating hematologic malignancies and solid tumors, VCR is recognized for inducing peripheral neuropathy and significantly affecting patient quality of life. The present review explores the current literature on the pathophysiological and molecular mechanisms underlying VCR-induced neurotoxicity. Mainly explore the effects of VCR on microtubule dynamics, axonal transport, calcium homeostasis, mitochondrial function, and neuroinflammatory pathways. Moreover, examine the pharmacogenetic factors and genetic polymorphisms such as CYP3A5 and ABCB1 that may influence individual susceptibility to VCR-induced peripheral neuropathy (VIPN). Also, the present review highlights critical insights into how VCR disrupts microtubule assembly, leading to axonal degeneration and neuronal dysfunction. Furthermore, neuroinflammation and mitochondrial dysfunction were found to exacerbate neuronal damage, underscoring the complex interplay of factors contributing to VIPN. So, understanding the molecular basis of VCR dysfunction is essential for developing strategies to mitigate VIPN while preserving the drug's antineoplastic efficacy and improving patient management in cancer treatment.
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