文章：

癌症多药耐药：ATP依赖转运体的作用

Multidrug resistance in cancer: role of ATP–dependent transporters

原文发布日期：2002-01-01

DOI: 1038/nrc706

类型: Review Article

开放获取: 否

要点：

1. Multidrug resistance of cancer cells is a potentially surmountable obstacle to effective chemotherapy of cancer.
2. ATP-binding cassette (ABC) transporters, including MDR1 (ABCB1), MRP1 (ABCC1) and ABCG2, can confer multidrug resistance to cancer cells in vitro.
3. MRP2 (ABCC2), MRP3 (ABCC3), MRP4 (ABCC4), MRP5 (ABCC5), ABCA2 and BSEP (ABCB11) are capable of transporting drugs; future studies are needed to determine a role in drug resistance.
4. ABC transporters such as MDR1 and MRP1 are expressed in many human cancers, including leukaemias and some solid tumours; in some studies, expression of these transporters has been shown to correlate with response to therapy and survival.
5. Inhibitors of ABC transporters such as MDR1/P-glycoprotein have been tested in clinical trials with a suggestion of benefit, especially in acute myelogenous leukaemia.
6. Interpretation of clinical trials using inhibitors of MDR1/P-glycoprotein has been confounded by their effects on the pharmacokinetics of anticancer drugs.
7. Development of inhibitors of ABC transporters should focus on potency and specificity to minimize unexpected pharmacokinetic effects.
8. Efficacy should be confirmed using surrogate assays.
9. Normal tissues might be protected from toxicity by gene transfer of drug-resistance genes.
10. Prevention of ABC transporter induction in cancer cells might help to avert drug resistance.

要点翻译：

1. 癌细胞的多药耐药性是癌症有效化疗中一个可能被克服的障碍。
2. ATP结合盒（ABC）转运蛋白，包括MDR1（ABCB1）、MRP1（ABCC1）和ABCG2，能在体外赋予癌细胞多药耐药性。
3. MRP2（ABCC2）、MRP3（ABCC3）、MRP4（ABCC4）、MRP5（ABCC5）、ABCA2和BSEP（ABCB11）具备药物转运能力；这些蛋白在耐药性中的作用仍需通过后续研究确认。
4. MDR1和MRP1等ABC转运蛋白在多种人类癌症中均有表达，包括白血病和某些实体肿瘤；部分研究表明这些转运蛋白的表达水平与治疗反应及生存率存在相关性。
5. MDR1/P-糖蛋白等ABC转运蛋白抑制剂的临床试验已显示一定疗效潜力，尤其在急性髓系白血病治疗中。
6. 由于MDR1/P-糖蛋白抑制剂对抗癌药物药代动力学存在影响，使得相关临床试验结果的解读变得复杂。
7. ABC转运蛋白抑制剂的研发应着重提升效力和特异性，以最大限度减少不可预见的药代动力学影响。
8. 应通过替代性检测方法验证抑制剂疗效。
9. 通过耐药基因的基因转移或可保护正常组织免受毒性损伤。
10. 阻止癌细胞中ABC转运蛋白的诱导表达可能有助于规避耐药性问题。

英文摘要：

Chemotherapeutics are the most effective treatment for metastatic tumours. However, the ability of cancer cells to become simultaneously resistant to different drugs — a trait known as multidrug resistance — remains a significant impediment to successful chemotherapy. Three decades of multidrug-resistance research have identified a myriad of ways in which cancer cells can elude chemotherapy, and it has become apparent that resistance exists against every effective drug, even our newest agents. Therefore, the ability to predict and circumvent drug resistance is likely to improve chemotherapy.

摘要翻译： 

化疗药物是治疗转移性肿瘤最有效的方法。然而，癌细胞同时对不同药物产生耐药性的能力——即所谓的多药耐药性——仍然是成功化疗的一大障碍。三十年的多药耐药性研究揭示了癌细胞逃避化疗的无数机制，并且显而易见的是，每一种有效药物，甚至是我们最新的药物，都存在耐药性。因此，预测并规避耐药性的能力可能会改善化疗效果。

原文链接：

Multidrug resistance in cancer: role of ATP–dependent transporters