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新一代铂类药物在顺铂耐药癌症治疗中的应用

New-generation platinum drugs in the treatment of cisplatin-resistant cancers.

作者信息

McKeage Mark J

机构信息

Department of Pharmacology and Clinical Pharmacology, School of Medical Sciences, The University of Auckland, Auckland, New Zealand.

出版信息

Expert Opin Investig Drugs. 2005 Aug;14(8):1033-46. doi: 10.1517/13543784.14.8.1033.

Abstract

Platinum drugs with altered stable ligands, such as oxaliplatin and satraplatin, produce a different DNA-adduct profile to cisplatin. This results in a distinct therapeutic profile, and clinical trials with these agents demonstrate significant anticancer activity in diseases with inherent or acquired resistance to cisplatin, such as colorectal and prostate cancers as well as previously treated ovarian and germ-cell cancer. An alternative approach to increasing the efficacy associated with platinum therapy is to enhance tumour delivery by coupling platinum drugs with a polymer or encapsulating the agent in a liposome. The early clinical trials of these novel delivery formulations are promising but, as yet, have not confirmed that the delivery of platinum to the tumour cell DNA is increased.

摘要

具有改变的稳定配体的铂类药物,如奥沙利铂和沙铂,产生与顺铂不同的DNA加合物谱。这导致了独特的治疗谱,并且用这些药物进行的临床试验表明,在对顺铂具有固有或获得性耐药性的疾病中,如结直肠癌、前列腺癌以及先前治疗过的卵巢癌和生殖细胞癌,具有显著的抗癌活性。提高铂类治疗疗效的另一种方法是通过将铂类药物与聚合物偶联或将药物包裹在脂质体中来增强肿瘤递送。这些新型递送制剂的早期临床试验很有前景,但尚未证实铂向肿瘤细胞DNA的递送增加。

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