Translational Research Institute, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar.
College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.
J Transl Med. 2018 Apr 11;16(1):96. doi: 10.1186/s12967-018-1471-1.
Cisplatin is a widely used chemotherapeutic agent for treatment of various cancers. However, treatment with cisplatin is associated with drug resistance and several adverse side effects such as nephrotoxicity, reduced immunity towards infections and hearing loss. A Combination of cisplatin with other drugs is an approach to overcome drug resistance and reduce toxicity. The combination therapy also results in increased sensitivity of cisplatin towards cancer cells. The mitogen activated protein kinase (MAPK) pathway in the cell, consisting of extracellular signal regulated kinase, c-Jun N-terminal kinase, p38 kinases, and downstream mediator p90 ribosomal s6 kinase (RSK); is responsible for the regulation of various cellular events including cell survival, cell proliferation, cell cycle progression, cell migration and protein translation. This review article demonstrates the role of MAPK pathway in cisplatin based therapy, illustrates different combination therapy involving cisplatin and also shows the importance of targeting MAPK family, particularly RSK, to achieve increased anticancer effect and overcome drug resistance when combined with cisplatin.
顺铂是一种广泛用于治疗各种癌症的化疗药物。然而，顺铂治疗与药物耐药性和几种不良反应相关，如肾毒性、抗感染能力下降和听力损失。将顺铂与其他药物联合使用是克服耐药性和降低毒性的一种方法。联合治疗还可增加顺铂对癌细胞的敏感性。细胞中的丝裂原激活蛋白激酶（MAPK）途径，由细胞外信号调节激酶、c-Jun N 端激酶、p38 激酶和下游介质 p90 核糖体 S6 激酶（RSK）组成；负责调节包括细胞存活、细胞增殖、细胞周期进程、细胞迁移和蛋白质翻译在内的各种细胞事件。本文综述了 MAPK 途径在顺铂为基础的治疗中的作用，说明了涉及顺铂的不同联合治疗方法，并展示了靶向 MAPK 家族，特别是 RSK，以在与顺铂联合使用时获得增强的抗癌效果和克服耐药性的重要性。
