New cisplatin analogues in development. A review

Area of Science:

• Oncology
• Medicinal Chemistry
• Pharmacology

Background:

• Cisplatin, a cornerstone in germ cell cancer treatment since the 1970s, exhibits significant cytotoxic properties.
• Thousands of cisplatin analogues have been synthesized, aiming to enhance its therapeutic index and overcome resistance.
• Carboplatin, the only approved analogue, reduces toxicity but does not overcome platinum resistance or broaden efficacy.

Purpose of the Study:

• To review the development of platinum analogues aimed at overcoming cisplatin resistance.
• To explore novel platinum complex designs targeting different DNA interactions and improved patient quality of life.
• To highlight platinum analogues currently in clinical trials for cancer treatment.

Main Methods:

• Review of preclinical and clinical studies on cisplatin analogues.
• Analysis of drug design strategies focusing on overcoming platinum resistance.
• Identification of platinum analogues undergoing clinical evaluation worldwide.

Main Results:

• Limited success in developing analogues with improved efficacy or broader spectrum compared to cisplatin.
• Carboplatin offers toxicity benefits but not resistance overcoming capabilities.
• Nine platinum analogues are in clinical trials, including 'third generation' complexes with potential for reduced cross-resistance.

Conclusions:

• Platinum resistance remains a major challenge in cancer chemotherapy.
• Ongoing research focuses on novel platinum analogues with diverse mechanisms of action and improved pharmacokinetic profiles.
• Several new platinum-based drugs show promise in clinical trials for enhanced anticancer efficacy and patient well-being.