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1965年,Rosenberg 发现了顺铂的抗肿瘤活性,1978年,引入临床研究之后,顺铂开始广泛应用于肿瘤治疗[1]。对于睾丸癌,顺铂有超过95%的治愈率,对于其他肿瘤,如卵巢癌、膀胱癌、头颈部癌和肺癌等也有一定疗效。继顺铂之后,卡铂、奥沙利铂、奈达铂、洛铂、庚铂等几种经典铂类化合物先后被研发出来,尽管铂类已成为临床上治疗肿瘤的一线化疗药物,但是,其严重的耐药性极大的限制了它的临床应用,因此,研究者们不断探索铂类药物的耐药机制,期望研发出低毒高效的新型铂类抗肿瘤药物。
Research progress and coping strategy of the drug resistant mechanism of platinum anti-tumor drugs
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摘要: 铂类抗肿瘤药物是目前临床应用最广泛的一线化疗药物,疗效显著。但临床使用过程中出现的非小细胞肺癌、乳腺癌、卵巢癌等铂类药物耐药问题,严重影响了铂类药物的疗效,也极大限制了铂类药物的使用。铂类药物耐药是由多种因素引起的,目前关于铂类药物的耐药机制主要有以下几个方面:减少细胞内铂的积累、促进细胞内铂的失活、DNA的损伤修复能力增强、肿瘤细胞凋亡抑制作用增强等。本文就铂类抗肿瘤药物的耐药机制和应对策略做一综述,为铂类抗肿瘤药物的研发提供思路,为克服临床铂类药物耐药问题提供参考。Abstract: Platinum anti-tumor drugs are currently the most widely used first-line chemotherapeutic drugs in clinical practice, and their curative effects are remarkable. However, the problems of platinum drug resistance in non-small cell lung cancer, breast cancer, ovarian cancer and others seriously limit effectiveness and clinical application of platinum drugs. The occurrence of platinum drug resistance is caused by many factors. At present, the resistance mechanism of platinum drugs mainly includes the following aspects: decreasing the accumulation of platinum in cells, increasing the inactivation of platinum in cells, repairing DNA damage and tumor cell apoptosis inactivation. This article reviews the drug resistance mechanism and coping strategy of platinum anti-tumor drugs, providing ideas for the development of platinum anti-tumor drugs and references for overcoming clinical platinum drug resistance.
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Key words:
- platinum drugs /
- anti-tumor drugs /
- drug resistance mechanism
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