ABC 转运体在体内平衡、癌症发病机制和治疗中的作用

S. Boichuk, T. V. Ivoilova
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摘要

ABC转运体(ATP结合盒(ABC)转运体)是一种蛋白质,在物质跨膜转运中扮演着双重角色。一方面,它们在细胞内转运营养物质和其他分子,以提供必要的营养物质;另一方面,这些蛋白质将一些内源性和外源性底物排出细胞,以维持体内平衡,防止受到侵袭性环境的影响。ABC 转运体在各种代谢紊乱的发病机制中扮演着重要角色。此外,已有大量证据表明,这些蛋白参与了肿瘤的发生、发展、侵袭和转移,以及多药耐药表型的形成。目前,这些蛋白是极具吸引力的治疗靶点,对它们施加影响可以显著提高抗癌治疗的效果,改善肿瘤疾病(包括复发性、转移性和无法手术的肿瘤)患者的预后。本综述提供了有关影响 ABC 转运体功能活性的药物及其作用机制的信息,还介绍了这些抑制剂的临床试验结果。
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The role of ABC-transporters in homeostasis, cancer pathogenesis and therapy
ABC transporters (ATP Binding Cassette (ABC) transporters) are proteins, which play a dual role in the substances transport across the membrane. On the one hand, they transport nutrients and other molecules inside the cell to supply the necessary nutrients, on the other hand, these proteins excrete some endogenous and exogenous substrates from the cell to maintain their homeostasis in the body and prevent from effects of aggressive environment. ABC transporters play a role in the pathogenesis of various metabolic disorders. In addition, a large amount of evidence has been accumulated about the participation of these proteins in oncogenesis because of their involvement into initiation, progression, invasion and metastasis of tumors, as well as development of multidrug resistance phenotype. Currently, these proteins are attractive therapeutic targets, influence on which can significantly increase the effectiveness of anticancer therapy and improve the prognosis of patients with oncological diseases, including recurrent, metastatic and inoperable forms.The review provides information on drugs that affect the functional activity of ABC transporters and the mechanisms of their action, and also presents the results of clinical trials of these inhibitors.
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