Platinum complexes and their anti-tumour activity against chronic lymphocytic leukaemia cells

Abstract

© 2015 University of Kragujevac, Faculty of Science. All rights reserved. Since the discovery of the antitumor activity of cisplatin by Rosenberg and co-workers, the use of metal complexes in cancer treatment has caused a huge interest. Today, platinum- based drugs are part of standard chemotherapy in the management of a variety of ca ncers, germ cell tumours, sarcomas, and lymphomas. Unfortunately, toxicity and drug resistance are major obstacles to wider clinical application of these drugs. Their use is greatly limited by severe side effects such as nephrotoxicity, ototoxicity, and neurotoxicity. Although cisplatin is one of the most successful anticancer drugs to date, its biochemical mechanism of action is still unclear. Cisplatin is generally accepted as having the ability to interact with the purine bases on the DNA, causing DNA damage, interfering with DNA repair mechanisms, and subsequently inducing apoptosis in cancer cells. Chronic lymphocytic leukaemia is a neoplastic B cell lymphoproliferative disease characterized by a highly variable clinical course. Clinical stage at the diagnosis and biological prognostic factors are the important predictors for survival. The Rai and Binet staging systems describe three major prognostic subgroups. Commonly used prognostic biomarkers in chronic lymphocytic leukaemia can be divided into genotypic, DNA-level changes and phenotypic, expression-level changes. For chronic lymphocytic leukaemia, substantial progress in therapy has not been made over the past 40 years. The main goal of future scientific research is to find new platinum complexes that have better efficacy in cancer treatment, the ability to be administered orally, without developing a cancer-drug resistance, and reduced toxic side effects.