多药耐药相关蛋白1基因在神经母细胞瘤生物学特性及临床预后中的作用。

The role of the multidrug resistance-associated protein 1 gene in neuroblastoma biology and clinical outcome.

作者信息

Pajic Marina, Norris Murray D, Cohn S L, Haber Michelle

机构信息

Children's Cancer Institute Australia for Medical Research, P.O. Box 81 Randwick, Sydney, NSW 2031, Australia.

出版信息

Cancer Lett. 2005 Oct 18;228(1-2):241-6. doi: 10.1016/j.canlet.2005.01.060.

DOI:10.1016/j.canlet.2005.01.060

PMID:15979785

Abstract

Multidrug resistance is a major obstacle to cancer treatment and leads to poor prognosis for the patient. Multidrug resistance-associated protein 1 (MRP1) can confer drug resistance in vitro and MRP1 may play a role in the development of drug resistance in several cancers including acute myeloid leukaemia, small cell lung cancer, T-cell leukaemia and 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 for the involvement of the MYCN oncogene, and its down-stream target, MRP1, 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.

摘要

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）可在体外赋予耐药性，并且MRP1可能在包括急性髓细胞白血病、小细胞肺癌、T细胞白血病和神经母细胞瘤在内的几种癌症的耐药性发展中起作用。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，这些患者的预后仍然很差。越来越多的证据表明，MYCN癌基因及其下游靶点MRP1参与了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。