Abstract
Platinum drugs are widely used in antitumour therapy and are a cornerstone of the treatment of different solid tumours. The pharmacological interest of cisplatin has led to the design of many analogues to broaden the spectrum of activity, reduce side effects, and overcome resistance. Although the cis configuration was initially identified as the only active one, trans-platinum complexes have shown significant antitumour activity in preclinical models. In addition to mononuclear platinum compounds, multinuclear platinum complexes have been generated that are characterised by a different mode of interaction with DNA. Since a major limitation to the clinical efficacy of platinum compounds is drug resistance, the most important feature of nonconventional platinum drugs should be the capability of overcoming cellular resistance. However, due to the multifactorial nature of clinical resistance, which also involves pharmacological factors, the optimisation of current platinum-based therapy also includes the development of drug delivery approaches. The present review focuses on recent studies on the molecular alterations of tumour cells that are associated with resistance to platinum drugs, the development of novel platinum drugs, and approaches that may contribute to improve the efficacy of platinum-based therapy.
Keywords: Cisplatin, oxaliplatin, polynuclear platinum compounds, drug resistance, drug delivery
Current Medicinal Chemistry
Title: Strategies to Improve the Efficacy of Platinum Compounds
Volume: 16 Issue: 19
Author(s): Giacomo Cossa, Laura Gatti, Franco Zunino and Paola Perego
Affiliation:
Keywords: Cisplatin, oxaliplatin, polynuclear platinum compounds, drug resistance, drug delivery
Abstract: Platinum drugs are widely used in antitumour therapy and are a cornerstone of the treatment of different solid tumours. The pharmacological interest of cisplatin has led to the design of many analogues to broaden the spectrum of activity, reduce side effects, and overcome resistance. Although the cis configuration was initially identified as the only active one, trans-platinum complexes have shown significant antitumour activity in preclinical models. In addition to mononuclear platinum compounds, multinuclear platinum complexes have been generated that are characterised by a different mode of interaction with DNA. Since a major limitation to the clinical efficacy of platinum compounds is drug resistance, the most important feature of nonconventional platinum drugs should be the capability of overcoming cellular resistance. However, due to the multifactorial nature of clinical resistance, which also involves pharmacological factors, the optimisation of current platinum-based therapy also includes the development of drug delivery approaches. The present review focuses on recent studies on the molecular alterations of tumour cells that are associated with resistance to platinum drugs, the development of novel platinum drugs, and approaches that may contribute to improve the efficacy of platinum-based therapy.
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Cossa Giacomo, Gatti Laura, Zunino Franco and Perego Paola, Strategies to Improve the Efficacy of Platinum Compounds, Current Medicinal Chemistry 2009; 16 (19) . https://dx.doi.org/10.2174/092986709788682083
DOI https://dx.doi.org/10.2174/092986709788682083 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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