Involvement of ABC transporters in melanogenesis and the development of multidrug resistance of melanoma.
Involvement of ABC transporters in melanogenesis and the development of multidrug resistance of melanoma.
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DOI：
10.1111/j.1755-148x.2009.00630.x
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发表时间：
2009-12
影响因子：
4.3
通讯作者：
Gottesman MM
中科院分区：
文献类型：
--
作者：
Chen KG;Valencia JC;Gillet JP;Hearing VJ;Gottesman MM
由于黑色素瘤本质上对常规放疗和化疗具有抗性，因此已经开发了许多替代治疗方法，例如生物化疗和免疫治疗。人类肿瘤多药耐药（MDR）的最常见原因是一种或多种ATP结合盒（ABC）转运蛋白的表达和功能，这些转运蛋白将抗癌药物从细胞中排出。黑色素瘤细胞表达一组ABC转运蛋白（如ABCA 9、ABCB 1、ABCB 5、ABCB 8、ABCC 1、ABCC 2和ABCD 1），这些转运蛋白可能与黑色素瘤细胞对广泛的抗癌药物的抗性和/或黑色素细胞对有毒黑色素中间体和代谢物的抗性相关。在这篇综述中，我们提出了一个模型（称为ABC-M模型），其中黑色素瘤细胞的内在MDR至少部分是由于转运系统，也可能发挥关键作用，在减少黑素细胞中的黑素生成途径的细胞毒性。ABC-M模型提出了在黑素生成途径的背景下逆转MDR功能的分子策略，这可能为最终实现规避黑色素瘤患者临床MDR的目标开辟治疗途径。
Because melanomas are intrinsically resistant to conventional radiotherapy and chemotherapy, many alternative treatment approaches have been developed such as biochemotherapy and immunotherapy. The most common cause of multidrug resistance (MDR) in human cancers is the expression and function of one or more ATP-binding cassette (ABC) transporters that efflux anticancer drugs from cells. Melanoma cells express a group of ABC transporters (such as ABCA9, ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, and ABCD1) that may be associated with the resistance of melanoma cells to a broad range of anticancer drugs and/or of melanocytes to toxic melanin intermediates and metabolites. In this review, we propose a model (termed the ABC-M model) in which the intrinsic MDR of melanoma cells is at least in part due to the transporter systems that may also play a critical role in reducing the cytotoxicity of the melanogenic pathway in melanocytes. The ABC-M model suggests molecular strategies to reverse MDR function in the context of the melanogenic pathway, which could open therapeutic avenues towards the ultimate goal of circumventing clinical MDR in patients with melanoma.