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【文摘发布】ABCG2与癌症临床耐药
Author: Robey RW, Polgar O, Deeken J, To KW, Bates SE.
Resource：Cancer Metastasis Rev. 2007 Mar;26(1):39-57
Impact Factor：8.0（2005）
Abstract：Multidrug resistance is a major obstacle to successful cancer treatment. One mechanism by which cells can become resistant to chemotherapy is the expression of ABC transporters that use the energy of ATP hydrolysis to transport a wide variety of substrates across the cell membrane. There are three human ABC transporters primarily associated with the multidrug resistance phenomenon, namely Pgp, MRP1, and ABCG2. All three have broad and, to a certain extent, overlapping substrate specificities, transporting the major drugs currently used in cancer chemotherapy. ABCG2 is the most recently described of the three major multidrug-resistance pumps, and its substrates include mitoxantrone, topotecan, irinotecan, flavopiridol, and methotrexate. Despite several studies reporting ABCG2 expression in normal and malignant tissues, no trials have thus far addressed the role of ABCG2 in clinical drug resistance. This gives us an opportunity to critically review the disappointing results of past clinical trials targeting Pgp and to propose strategies for ABCG2. We need to know in which tumor types ABCG2 contributes to the resistance phenotype. We also need to develop standardized assays to detect ABCG2 expression in vivo and to carefully select the chemotherapeutic agents and clinical trial designs. This review focuses on our current knowledge about normal tissue distrubution, tumor expression profiles, and substrates and inhibitors of ABCG2, together with lessons learned from clinical trials with Pgp inhibitors. Implications of SNPs in the ABCG2 gene affecting the pharmacokinetics of substrate drugs, including many non-chemotherapy agents and ABCG2 expression in the SP population of stem cells are also discussed.
PMID: 17323127 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 Title：ABCG2: determining its relevance in clinical drug resistance
ABCG2与临床耐药
Author: Robey RW, Polgar O, Deeken J, To KW, Bates SE.
Resource：Cancer Metastasis Rev. 2007 Mar;26(1):39-57
Impact Factor：8.0（2005）
Abstract：Multidrug resistance is a major obstacle to successful cancer treatment. One mechanism by which cells can become resistant to chemotherapy is the expression of ABC transporters that use the energy of ATP hydrolysis to transport a wide variety of substrates across the cell membrane. There are three human ABC transporters primarily associated with the multidrug resistance phenomenon, namely Pgp, MRP1, and ABCG2. All three have broad and, to a certain extent, overlapping substrate specificities, transporting the major drugs currently used in cancer chemotherapy. ABCG2 is the most recently described of the three major multidrug-resistance pumps, and its substrates include mitoxantrone, topotecan, irinotecan, flavopiridol, and methotrexate.
多药耐药是阻碍癌症治疗成功的主要障碍。细胞能够对化疗耐药的一个机制是，表达ABC转运体，从而利用ATP水解产生的能量将一系列的底物经过细胞膜进行转运。现在已经发现三个人类的ABC转运体与多药耐药相关，这三个转运体是Pgp、MRP1和ABCG2。这三个转运体的转运底物特异性都很广，而且在一定程度上重叠，能够转运当前癌症化疗中的主要药物。ABCG2是这三种多药耐药泵中最新近才发现的，它的转运底物包括米托蒽醌、拓扑替康、伊诺替康、flavopiridol和氨甲蝶呤。
Despite several studies reporting ABCG2 expression in normal and malignant tissues, no trials have thus far addressed the role of ABCG2 in clinical drug resistance. This gives us an opportunity to critically review the disappointing results of past clinical trials targeting Pgp and to propose strategies for ABCG2. We need to know in which tumor types ABCG2 contributes to the resistance phenotype. We also need to develop standardized assays to detect ABCG2 expression in vivo and to carefully select the chemotherapeutic agents and clinical trial designs. This review focuses on our current knowledge about normal tissue distrubution, tumor expression profiles, and substrates and inhibitors of ABCG2, together with lessons learned from clinical trials with Pgp inhibitors. Implications of SNPs in the ABCG2 gene affecting the pharmacokinetics of substrate drugs, including many non-chemotherapy agents and ABCG2 expression in the SP population of stem cells are also discussed.
虽然多项研究报道在正常和恶性组织中ABCG2表达，但是没有任何临床试验表明ABCG2在临床耐药上起作用。这让我们有机会对过去靶定Pgp的临床试验的令人失望的结果进行综述，并为靶定ABCG2提出一些策略。我们需要知道ABCG2在那些肿瘤中与耐药性有关。我们也需要发展一种标准的测试，用以在体检测ABCG2的表达，并且仔细的选择化疗药物、设计临床试验。本综述聚焦于关于ABCG2的正常组织分布、肿瘤表达谱、底物和抑制物等的当前认识，同时也说明了从Pgp抑制物的临床试验中得到的教训。本文还讨论了，ABCG2基因的SNPs影响底物药物的药物动力学，包括很多非化疗药物和干细胞的侧群细胞中ABCG2的表达。 不错，谢谢！！ [标签:content1][标签:content2]
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作者:admin@医学,生命科学 2011-04-15 05:11
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