He Miao, Wei Min-Jie
Department of Pharmacology, Pharmaceutical College of China Medical University, Shenyang, Liaoning 110001, P. R. China.
Chin J Cancer. 2012 Mar;31(3):126-33. doi: 10.5732/cjc.011.10315. Epub 2012 Jan 9.
Recently, a large number of tyrosine kinase inhibitors(TKIs) have been developed as anticancer agents. These TKIs can specifically and selectively inhibit tumor cell growth and metastasis by targeting various tyrosine kinases and thereby interfering with cellular signaling pathways. The therapeutic potential of TKIs has been hindered by multidrug resistance(MDR), which is commonly caused by overexpression of ATP-binding cassette(ABC) membrane transporters. Interestingly, some TKIs have also been found to reverse MDR by directly inhibiting the function of ABC transporters and enhancing the efficacy of conventional chemotherapeutic drugs. In this review, we discuss ABC transporter-mediated MDR to TKIs and MDR reversal by TKIs.
近年来，大量酪氨酸激酶抑制剂（TKIs）已被开发用作抗癌药物。这些TKIs可通过靶向各种酪氨酸激酶，特异性且选择性地抑制肿瘤细胞生长和转移，从而干扰细胞信号通路。多药耐药性（MDR）阻碍了TKIs的治疗潜力，MDR通常由ATP结合盒（ABC）膜转运蛋白的过表达引起。有趣的是，还发现一些TKIs可通过直接抑制ABC转运蛋白的功能和增强传统化疗药物的疗效来逆转MDR。在本综述中，我们讨论ABC转运蛋白介导的对TKIs的MDR以及TKIs对MDR的逆转作用。
