General reviewPlatinum anticancer drugs. From serendipity to rational designLes dérivés du platine en cancérologie. De la sérendipité à l’innovation rationnelle
Introduction
In 1963, Barnett Rosenberg (familiarly Barney), a biophysic professor at Michigan State University, initiated the research than led to the discovery of cis-platin. He decided with the help of his laboratory technician, Loretta Van Camp to examine the effects of an electric field on dividing Escherichia coli bacteria. This idea started from the fact that Barney noted a visual similarity of the pattern characteristic of the separation of chromosomes in the telophase of mammalian cell division and that of the lines of force between the poles of a magnet. He subsequently deduced that cell division might be affected by the magnetic component of an electrical field. Two platinum electrodes were used to generate the electric field. As well as the field was generated, the bacteria has undergone filamentous growth. Thus Barney observed that cell division was inhibited but not cell growth [1]. The experiments were reproduced several times while varying the electric field. Barney realized that a causative agent was produced which might be a useful anticancer agent. This was later identified as the cis-diaminodichloroplatinum or cis-platin resulting from the combination of platin with electrolytic products. Such a compound was already known since a long time and commonly designed as sel de Peyrone, Michele Peyrone (1813–1883) being the Italian chemist who prepared it for the first time in 1845. In 1968, Barney tested the cis-platin in Sarcoma 180 solid tumor mice implanted. Instead of treating the mice on the day after the tumor was implanted, Barney waited until the tumor had grown to about 1 g in weight. Serendipity again, this produced a high percentage of complete cures [2]. The potent antitumor activity of cis-platin was next evaluated by the National Cancer Institute and cis-platin entered clinical trials in 1971 in several locations. It was approved by the FDA in 1978.
Section snippets
Cis-platin
The introduction of cis-platin into the clinical treatment of cancer has resulted in dramatic improvements with regard to several tumor types such as testicular and ovarian carcinoma.
Indeed cis-platin is one of the most effective cancer agents, especially for testicular cancer, for which the overall cure rate exceeds 90%, and is nearly 100% for early-stage disease. It has been also indicated for treatment of cervical, head and neck, and non-small cell lung cancer. However, its administration is
Conclusions
In attempts to overcome the drawbacks of cis-platin – severe toxicity, drug resistance and poor oral bioavailability – the development of platinum-based drugs has progressed from carboplatin and oxaliplatin to the newest generation of drugs, such as satraplatin, picoplatin and the multinuclear platinum complex BBR3464 (triplatin) along with new formulation as lipoplatin and platin-containing polymer. Despite incontestable progress in the treatment of testicular cancers, platin derivatives
Disclosure of interest
The author declares that he has no conflicts of interest concerning this article.
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