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Tumour-inhibiting platinum complexes--state of the art and future perspectives
M A Jakupec1, M S Galanski, B K Keppler
1Institute of Inorganic Chemistry, University of Vienna, Währinger Strasse 42, 1090, Vienna, Austria.
Abstract:
Thirty years after the onset of the first clinical studies with cisplatin, the development of antineoplastic platinum drugs continues to be a productive field of research. This article reviews the current preclinical and clinical status, including a discussion of the molecular basis for the activity of the parent drug cisplatin and platinum drugs of the second and third generation, in particular their interaction with DNA. Further emphasis is laid on the development of third generation platinum drugs with activity in cisplatin-resistant tumours, particularly on chelates containing 1,2-diaminocyclohexane (DACH) and on the promising and more recently evolving field of non-classic ( trans- and multinuclear) platinum complexes. The development of oral platinum drugs and drug targeting strategies using liposomes, polymers or low-molecular-weight carriers in order to improve the therapeutic index of platinum chemotherapy are also covered.
Insights
Platinum-based chemotherapy continues to evolve, with new drug generations and delivery methods enhancing efficacy against resistant cancers. Research focuses on novel platinum complexes and targeted delivery to improve patient outcomes.
Area of Science:
- Oncology
- Pharmacology
- Medicinal Chemistry
Background:
- Cisplatin, a foundational platinum-based chemotherapy drug, has been studied for over 30 years.
- The development of platinum antineoplastic drugs remains an active area of research.
- Understanding the molecular mechanisms, particularly DNA interaction, is crucial for drug development.
Purpose of the Study:
- To review the preclinical and clinical status of platinum-based chemotherapy.
- To discuss the molecular basis of cisplatin and newer platinum drug activity.
- To highlight advancements in overcoming cisplatin resistance and improving drug delivery.
Main Methods:
- Review of existing preclinical and clinical research on platinum drugs.
- Analysis of molecular mechanisms, including DNA-drug interactions.
- Examination of novel platinum complex designs and drug delivery systems.
Main Results:
- Second and third-generation platinum drugs show improved activity and reduced resistance.
- Specific focus on 1,2-diaminocyclohexane (DACH) chelates and non-classic platinum complexes for resistant tumors.
- Development of oral platinum formulations and targeted delivery strategies (liposomes, polymers) to enhance therapeutic index.
Conclusions:
- Platinum drug development is a dynamic field with ongoing innovation.
- Newer platinum agents and delivery strategies offer promise for improved cancer treatment.
- Continued research is essential for optimizing platinum chemotherapy efficacy and patient care.