University of Montreal, Maisonneuve-Rosemont Hospital, Research Center, 5415, Boul. de l'Assomption, Montreal, Quebec, Canada, H1T 2M4, Canada.
Curr Drug Metab. 2010 Sep;11(7):595-602. doi: 10.2174/138920010792927307.
Bleomycin is a potent chemotherapeutic agent that can mediate cell killing by attacking the DNA. It is used in combination with other antineoplastic agents to effectively treat lymphomas, testicular carcinomas and squamous cell carcinomas of the cervix, head and neck. However, resistance to bleomycin remains a persistent limitation in exploiting the full therapeutic benefit of the drug for other types of cancers. Herein, we review recent findings from both yeast and human cells showing that uptake of bleomycin-A5 is a key mechanism that limits toxicity of the drug. We also discuss how the mammalian transporter hCT2 (SLC22A16) could be used to predict the outcome of tumor responses towards bleomycin therapy, and highlight the importance of further exploring this permease with respect to its regulation and pharmacological substrates for treating a wide range of cancers.
博来霉素是一种有效的化疗药物，能够通过攻击 DNA 来介导细胞杀伤。它与其他抗肿瘤药物联合使用，可有效治疗淋巴瘤、睾丸癌和宫颈癌、头颈部鳞状细胞癌。然而，对博来霉素的耐药性仍然是充分发挥该药治疗其他类型癌症疗效的一个持续限制因素。在此，我们综述了酵母和人类细胞的最新发现，表明博来霉素-A5 的摄取是限制药物毒性的关键机制。我们还讨论了哺乳动物转运蛋白 hCT2（SLC22A16）如何用于预测肿瘤对博来霉素治疗反应的结果，并强调进一步研究该渗透酶及其调节和药理学底物在治疗广泛的癌症方面的重要性。
