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ABC转运蛋白、耐药性与癌症干细胞

ABC transporters, drug resistance, and cancer stem cells.

作者信息

Dean Michael

机构信息

Laboratory of Experimental Immunology, Cancer and Inflammation Program, National Cancer Institute, Frederick, MD 21702, USA.

出版信息

J Mammary Gland Biol Neoplasia. 2009 Mar;14(1):3-9. doi: 10.1007/s10911-009-9109-9. Epub 2009 Feb 18.

Abstract

The protection of the body's stem cells from damage or death due to toxins is a critical function of an organism, as the stem cells need to remain intact for the entire life of the organism. One of the principal mechanisms for protecting stem cells is through the expression of multifunctional efflux transporters from the ATP-binding cassette (ABC) gene family. These same transporters have been known for over 25 years to also play a role in multidrug resistance of tumor cells. An exciting outcome of the concept of the cancer stem cell is that the tumor initiating cell may be innately resistant to many standard therapies. This provides one mechanism in which cancer stem cells could survive cytotoxic or targeted therapies and lead to tumor regrowth or relapse. Gaining a better insight into the mechanisms of stem cell resistance to chemotherapy might therefore lead to new therapeutic targets and better anti-cancer strategies.

摘要

保护机体干细胞免受毒素损害或死亡是生物体的一项关键功能,因为干细胞需要在生物体的整个生命周期中保持完整。保护干细胞的主要机制之一是通过ATP结合盒(ABC)基因家族中多功能外排转运蛋白的表达。25多年来人们一直知道,这些相同的转运蛋白在肿瘤细胞的多药耐药性中也起作用。癌症干细胞概念的一个令人兴奋的结果是,肿瘤起始细胞可能天生对许多标准疗法具有抗性。这提供了一种机制,癌症干细胞可借此在细胞毒性或靶向治疗中存活下来,并导致肿瘤再生或复发。因此,更好地了解干细胞对化疗的抗性机制可能会带来新的治疗靶点和更好的抗癌策略。

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