Sivadas Swathi Krishna, Das Aiswarya, Vijayakumar Nandana, Shaji Nandana, Mangalath Sabitha, Pavithran Keechilat, Biswas Lalitha
AmritaCenter for Nanosciences and Molecular medicine, Amrita Vishwa Vidyapeetham, Kochi, Kerala, India.
Department of Pharmaceutics, Amrita School of Pharmacy, Kochi, Kerala, India.
Drug Metab Rev. 2025 May;57(2):190-207. doi: 10.1080/03602532.2025.2485055. Epub 2025 Mar 31.
Paclitaxel is a widely used chemotherapeutic agent recognized for its efficacy against various malignancies. However, its clinical utility is often limited by paclitaxel-induced peripheral neuropathy (PIPN), a dose-dependent and debilitating side effect that significantly impacts patient quality of life. Genetic predisposition plays a critical role in individual susceptibility to PIPN, influencing both drug metabolism and neuropathic responses. This review examines the genetic basis of PIPN, focusing on polymorphisms in key genes associated with paclitaxel metabolism, transport, neuroinflammation, and neuronal signaling. Variants in , , and affect drug metabolism, while polymorphisms in and influence drug transport. Genes involved in neuroinflammatory pathways (, , ), peripheral nerve integrity (, ), and neuronal signaling () have also been implicated in PIPN susceptibility. Understanding genetic contributions to PIPN is essential for unraveling its pathophysiology and developing targeted interventions. Integrating genetic markers into clinical practice can facilitate personalized treatment strategies, minimizing PIPN risk and enhancing therapeutic outcomes. Further studies are needed to validate these findings across diverse populations and uncover novel genetic determinants.
紫杉醇是一种广泛使用的化疗药物，因其对各种恶性肿瘤的疗效而得到认可。然而，其临床应用常常受到紫杉醇诱导的周围神经病变（PIPN）的限制，这是一种剂量依赖性且使人衰弱的副作用，会显著影响患者的生活质量。遗传易感性在个体对PIPN的易感性中起着关键作用，影响药物代谢和神经病变反应。本综述探讨了PIPN的遗传基础，重点关注与紫杉醇代谢、转运、神经炎症和神经元信号传导相关的关键基因中的多态性。 、 和 中的变体影响药物代谢，而 和 中的多态性影响药物转运。参与神经炎症途径（ 、 、 ）、周围神经完整性（ 、 ）和神经元信号传导（ ）的基因也与PIPN易感性有关。了解遗传因素对PIPN的影响对于阐明其病理生理学和开发针对性干预措施至关重要。将遗传标记物整合到临床实践中可以促进个性化治疗策略，将PIPN风险降至最低并提高治疗效果。需要进一步研究以在不同人群中验证这些发现并发现新的遗传决定因素。
