Mechanisms of resistance of human tumours to anticancer drugs of the platinum family: a review.

The introduction of cisplatin and its less toxic analog carboplatin into anticancer chemotherapy regimens has greatly improved the initial response rate of various solid tumours, including squamous cell carcinoma of the head and neck. However, relapse of a drug-resistant tumour occurs with a high frequency, and remains the greatest impediment to successful chemotherapy treatment. Studies of cultured, drug-selected, resistant cell lines from numerous laboratories have suggested a variety of potential mechanisms of resistance, the most common of which are (1) reduced intracellular accumulation of drug, (2) enhanced removal of platinum adducts from DNA, (3) increased cellular glutathione, and (4) increased cellular metallothionein. This article describes the contribution of each of these mechanisms at a molecular level. By identifying markers or assays for each of these phenotypes, the importance of each as a mechanism of resistance in patient tumours can be ascertained. Then, methods of circumventing resistance can be utilized, with the intent of improving the success of platinum chemotherapy against squamous cell carcinoma in the head and neck.