Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Curr Pharm Biotechnol. 2011 Apr;12(4):595-608. doi: 10.2174/138920111795163913.
ABCG2, or breast cancer resistance protein (BCRP), is an ATP-binding cassette half transporter that has been shown to transport a wide range of substrates including chemotherapeutics, antivirals, antibiotics and flavonoids. Given its wide range of substrates, much work has been dedicated to developing ABCG2 as a clinical target. But where can we intervene clinically and how can we avoid the mistakes made in past clinical trials targeting P-glycoprotein? This review will summarize the normal tissue distribution, cancer tissue expression, substrates and inhibitors of ABCG2, and highlight the challenges presented in exploiting ABCG2 in the clinic. We discuss the possibility of inhibiting ABCG2, so as to increase oral bioavailability or increase drug penetration into sanctuary sites, especially the central nervous system; and at the other end of the spectrum, the possibility of improving ABCG2 function, in the case of gout caused by a single nucleotide polymphism. Together, these aspects of ABCG2/BCRP make the protein a target of continuing interest for oncologists, biologists, and pharmacologists.
ABCG2，也称为乳腺癌耐药蛋白（BCRP），是一种 ATP 结合盒半转运体，已被证明可转运多种底物，包括化疗药物、抗病毒药物、抗生素和类黄酮。鉴于其广泛的底物，许多工作致力于将 ABCG2 开发为临床靶点。但是，我们可以在临床上进行干预的地方在哪里，以及我们如何避免过去针对 P-糖蛋白的临床试验中犯的错误？本文综述了 ABCG2 的正常组织分布、癌组织表达、底物和抑制剂，并强调了在临床中利用 ABCG2 所面临的挑战。我们讨论了抑制 ABCG2 的可能性，以增加口服生物利用度或增加药物渗透到避难部位，特别是中枢神经系统；在另一方面，提高 ABCG2 功能的可能性，例如由单核苷酸多态性引起的痛风。综上所述，ABCG2/BCRP 的这些方面使该蛋白成为肿瘤学家、生物学家和药理学家持续关注的目标。
