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Web End = Cancer Chemother Pharmacol (2016) 77:11031124
DOI 10.1007/s00280-016-2976-z
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Web End = Platinumbased drugs: past, present and future
Shahana Dilruba1 Ganna V. Kalayda1
Received: 31 August 2015 / Accepted: 20 January 2016 / Published online: 17 February 2016 Springer-Verlag Berlin Heidelberg 2016
Cisplatin, the rst platinum anticancer drug
Cisplatin, cis-diamminedichloroplatinum(II) (Fig. 1), is known as Peyrones chloride since the end of nineteenth century (named after Michele Peyrone, who synthesized it rst). The cytostatic property of cisplatin was discovered by Barnett Rosenberg in the late 1960s, while he was doing experiments to analyze the effect of electric eld on bacterial growth. He observed that bacterial proliferation was ceased and pinned down the cause of this phenomenon to the platinum electrode that was used. Rosenberg and colleagues identied cisplatin as a key compound responsible for the anti-proliferative effect. Clinical trials were initiated in 1971, and after circumventing a number of obstacles, cisplatin was nally approved for use in testicular and ovarian cancer by the US Food and Drug Administration and in several European countries in 1979 [1].
Cisplatin is active against a wide spectrum of solid neoplasms, including ovarian, testicular, bladder, colorectal, lung and head and neck cancers [2, 3]. The drug often leads to an initial therapeutic response associated with complete disease remission, partial response or disease stabilization. However, cisplatin therapy requires additional medication and is accompanied by severe side effects including dose-limiting nephrotoxicity, cumulative peripheral sensory neuropathy, ototoxicity due to irreversible damage of the hair cells in Corti organ, as well as nausea and vomiting. Furthermore, resistance to cisplatin represents a major hurdle to the success of the treatment. Many tumors are intrinsically resistant to the platinum drug. Moreover, many originally sensitive tumors develop resistance gradually after initial response [4].
Abstract Platinum-based drugs cisplatin, carboplatin and oxaliplatin are widely used in the therapy of human neoplasms. Their clinical success is, however, limited due to severe side effects and intrinsic or acquired resistance to the treatment. Much effort has been put into the development of new platinum anticancer complexes, but none of them...