title: Platinum-based drugs: past, present and future.
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 has reached worldwide clinical application so far. Nedaplatin, lobaplatin and heptaplatin received only regional approval. Some new platinum complexes and platinum drug formulations are undergoing clinical trials. Here, we review the main classes of new platinum drug candidates, such as sterically hindered complexes, monofunctional platinum drugs, complexes with biologically active ligands, trans-configured and polynuclear platinum complexes, platinum(IV) prodrugs and platinum-based drug delivery systems. For each class of compounds, a detailed overview of the mechanism of action is given, the cytotoxicity is compared to that of the clinically used platinum drugs, and the clinical perspectives are discussed. A critical analysis of lessons to be learned is presented. Finally, a general outlook regarding future directions in the field of new platinum drugs is given.
authors.affiliation: Department of Clinical Pharmacy, Institute of Pharmacy, University of Bonn, An der Immenburg 4, 53121, Bonn, Germany.
authors.forename: Shahana
authors.initials: S
authors.lastname: Dilruba
authors.affiliation: Department of Clinical Pharmacy, Institute of Pharmacy, University of Bonn, An der Immenburg 4, 53121, Bonn, Germany. akalayda@uni-bonn.de.
authors.forename: Ganna V
authors.initials: GV
authors.lastname: Kalayda
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D055808:Drug Discovery / Q000379:methods / Q000639:trends; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D017671:Platinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D009944:Organoplatinum Compounds; D017671:Platinum Compounds
keywords: Clinical perspective; Future directions; Platinum drugs; Resistance; Toxicity