The state-of-play and future of platinum drugs

Abstract

The year 2015 marks the 50th anniversary since the discovery of the anticancer potential of cisplatin and it remains just as useful now as it did back then, especially for the treatment of some endocrine-related cancers like ovarian and testicular carcinomas. Since its discovery, five other platin drugs have received approval in various countries. While several new platin drugs are in preclinical development, in the last decade only two new platin drugs have entered clinical trials, LA-12 and dicycloplatin, reflecting a shift in research focus from new drug design to improved formulations of already approved platin drugs. These formulations include their encapsulation with macrocycles to slow and prevent their degradation by proteins and peptides; their attachment to nanoparticles to passively target solid tumours through the enhanced permeability and retention effect and their coordination to important nutrients, proteins, antibodies and aptamers for active tumour targeting. These formulation methods have all shown potential but none have yet yielded a new marketable medicine containing a platin drug. The reasons for this are problems of consistent drug loading, controlling the location and timing of drug release and the inherent toxicity of some of the drug delivery vehicles. In addition to drug delivery, functional genomics is now playing an increasing role in predicting patients' responses to platin chemotherapy and their likelihood of experiencing severe side effects.

Polymeric nanoparticles for colon cancer therapy: overview and perspectives

“…In contrast to other platinum-based drugs like cisplatin and carboplatin, oxaliplatin is a third-generation platinum compound which features the ligand 1,2-diaminocyclohexane in place of the two monodentate amine ligands. 50 Like other platinum-based drugs, oxaliplatin fights colon cancer through non-targeted cytotoxic effects, specifically forming both inter-and intra-strand cross links in DNA, thus inhibiting the replication and transcription of DNA. 51 Irinotecan is a semi-synthetic analogue of the natural camptothecin and can act as an inhibitor of topoisomerase 1 for cancer therapy.…”

Pt(IV)/Re(I) Chitosan Conjugates as a Flexible Platform for the Transport of Therapeutic and/or Diagnostic Anticancer Agents

“…Finally, the resulting conjugate C123 was used to coordinate the fac-[Re(CO) 3 [39,40], to give the conjugate C1234. The whole synthetic pathway is reported in Scheme 3.…”

“…Since then, this simple Pt(II) compound has become one of the most widely used chemotherapeutic agents. It is best known for curing testicular cancer, but it is also used in the treatment of a wide range of other cancers, including lung, bladder, cervical, and ovarian cancers, alone or in combination with other drugs [1][2][3].…”

Ototoxicity: Old and New Foes

“…• loop diuretics Platinum-based cytostatics (cisplatin, carboplatin and oxaliplatin) are used as single agents and in combination with other drugs for the treatment of various types of cancer (e.g., testicular carcinoma, lung carcinoma, ovarian carcinoma, head and neck carcinomas, melanomas, lymphomas and neuroblastomas) [8]. The platinum-based drugs bind DNA and induce irreversible changes that prohibit tumor cell division.…”