The Role of the Platinum Derivatives in Cancer Therapy

The discovery of cisplatinum and the subsequent development of its derivatives (carboplatin and oxaliplatin) represent an interesting saga in modern oncology. When Rosenberg observed in 1960s that platinum electrodes in salt water baths inhibited the growth of bacteria and fungi it lead to the isolation of cis-dichloro diamine platinum (cisplatin). Its application in testicular cancer provided a dramatic leap forward for this heretofore-lethal disease. Subsequent applications in ovary and lung cancers lead to some of the most effective therapies in modern oncology. Although the exact mechanisms of action continue to be investigated, the platination of guanine residues in DNA constitutes the principle mechanism of cytotoxicity.

The use of the human tumor laboratory model has provided us the luxury of exploring the platinum drugs in a wide variety of diseases. Among our published discoveries has been the relative equivalence of the platinum derivatives, as well as their profound synergy with agents like gemcitabine. It is of significant interest that this broadly effective class of compounds — extensively applied in the treatment of lung, colorectal, ovarian and breast cancers, as well as others — remains less active in the hematologic neoplasms. This is in striking counter distinction to nearly all other classes of chemotherapeutics.

Among our most gratifying observations, from the early 1990s, was the clear and profound activity of the platinum derivatives in breast cancers. We feel that our discoveries, outlined in an editorial published in 2000 (The Once and Future Role of Platinum Agents in Advanced Breast Cancer), in no small part have influenced the broad application of platinum in modern breast cancer management.

It was not genius or divine intervention that lead us to these important discoveries, but, quite simply, the use of a validated human tumor model that accurately probed tumor types, leading us to these findings. It is virtually impossible for an unbiased observer to review these contributions and not recognize that the human tumor model has been the conduit by which these discoveries were made.

The proper study of human cancer is human cancer. Our results speak for themselves when it comes to ovarian, breast and hematologic neoplasms, treatments for which can be traced directly to our laboratories.