Munoz Marcia, Henderson Michelle, Haber Michelle, Norris Murray
Children's Cancer Institute Australia for Medical Research, Sydney, NSW, Australia.
IUBMB Life. 2007 Dec;59(12):752-7. doi: 10.1080/15216540701736285.
Multidrug resistance is a major obstacle to cancer treatment and leads to poor prognosis for the patient. Multidrug resistance-associated protein 1 (MRP1) transports a wide range of therapeutic agents as well as diverse physiological substrates and may play a role in the development of drug resistance in several cancers including those of the lung, breast and prostate, as well as childhood neuroblastoma. The majority of patients with neuroblastoma present with widely disseminated disease at diagnosis and despite intensive treatment, the prognosis for such patients is dismal. There is increasing evidence that MRP1 is a MYCN target gene involved in the development of multidrug resistance in neuroblastoma. Given the importance of MRP1 overexpression in neuroblastoma, MRP1 inhibition may be a clinically relevant approach to improving patient outcome in this disease.
多药耐药是癌症治疗的主要障碍,会导致患者预后不良。多药耐药相关蛋白1(MRP1)可转运多种治疗药物以及多种生理底物,可能在包括肺癌、乳腺癌、前列腺癌以及儿童神经母细胞瘤在内的多种癌症的耐药性发展中发挥作用。大多数神经母细胞瘤患者在诊断时就已出现广泛播散性疾病,尽管进行了强化治疗,这些患者的预后依然很差。越来越多的证据表明,MRP1是一个MYCN靶基因,参与神经母细胞瘤多药耐药的发展。鉴于MRP1过表达在神经母细胞瘤中的重要性,抑制MRP1可能是改善该疾病患者预后的一种具有临床相关性的方法。