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Loss of oatp1b3 function causes rotor syndrome: Implications for potential use of inhibitors in cancer

机译:oatp1b3功能丧失导致转子综合征:潜在使用抑制剂治疗癌症的意义

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摘要

There has been increasing recognition that organic anion transporter proteins (OATPs) play an important role in the biology of various cancers. De novo expression of OATPs has been identified in breast, colon, pancreatic, gastric and prostate cancer cells, among others.1 In patients with prostate cancer, polymorphisms encoding decreased functioning OATP1B3 were associated with a longer time to progression on androgen deprivation therapy and a longer overall survival which is likely caused by reduced tumoral testosterone uptake.2-4 Because of these findings, therapeutic inhibition targeting OATP1B3 has been proposed. However, any enthusiasm for inhibiting OATP1Bs therapeutically has been tempered by reservations about potential consequences. For instance, inhibitors could interfere with several normal physiological processes mediated by OATP1B3 (i.e., bile acid reuptake, bilirubin uptake, etc) or cause potential, as-yet unknown, drug interactions by barring hepatic uptake, subsequent metabolism and elimination.
机译:人们日益认识到,有机阴离子转运蛋白(OATP)在各种癌症的生物学中起着重要作用。已在乳腺癌,结肠癌,胰腺癌,胃癌和前列腺癌等细胞中鉴定了OATP的从头表达。1在前列腺癌患者中,编码功能降低的OATP1B3的多态性与雄激素剥夺治疗的进展时间更长有关。由于肿瘤睾丸激素摄取减少,可能导致更长的总生存期。2-4由于这些发现,有人提出了针对OATP1B3的治疗性抑制作用。但是,对于抑制OATP1Bs的任何治疗热情都因对潜在后果的保留而减弱。例如,抑制剂可能会干扰由OATP1B3介导的几种正常生理过程(即胆汁酸再摄取,胆红素摄取等)或通过禁止肝摄取,随后的代谢和消除而引起潜在的,尚未见的药物相互作用。

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