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Platinum-based drugs: past, present and future
Shahana Dilruba1, Ganna V Kalayda2
1Department of Clinical Pharmacy, Institute of Pharmacy, University of Bonn, An der Immenburg 4, 53121, Bonn, Germany.
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.
Insights
New platinum anticancer drugs aim to overcome resistance and side effects of current treatments like cisplatin. Research focuses on novel complexes and drug delivery systems for improved cancer therapy.
Area of Science:
- Oncology
- Medicinal Chemistry
- Drug Development
Background:
- Platinum-based drugs (cisplatin, carboplatin, oxaliplatin) are mainstays in cancer treatment.
- Clinical efficacy is hampered by severe side effects and drug resistance.
- Existing platinum drugs have limitations, necessitating new therapeutic agents.
Purpose of the Study:
- To review emerging classes of platinum anticancer drug candidates.
- To analyze their mechanisms of action, cytotoxicity, and clinical potential.
- To provide an outlook on future directions in platinum drug development.
Main Methods:
- Literature review of novel platinum anticancer complexes.
- Analysis of drug classes including sterically hindered, monofunctional, and platinum(IV) complexes.
- Evaluation of platinum-based drug delivery systems and their clinical perspectives.
Main Results:
- Several new classes of platinum drugs are under investigation, including platinum(IV) prodrugs and targeted delivery systems.
- These novel agents aim to improve efficacy and reduce toxicity compared to existing platinum drugs.
- Some agents show promise but require further clinical validation.
Conclusions:
- Despite challenges, ongoing research into novel platinum complexes and formulations offers potential for improved cancer treatment.
- Addressing drug resistance and side effects remains a key focus for next-generation platinum anticancer agents.
- Future directions include exploring platinum(IV) prodrugs and advanced drug delivery systems for enhanced therapeutic outcomes.