Topoisomerases and tubulin inhibitors: a promising combination for cancer treatment.

Abstract

Modern approaches to treatment of cancer seek to activate the internal suicide program in the malignant cells, and thereby effectively eliminate them without engaging most of other bodily systems. Many currently used cytostatics are known to induce apoptosis and efforts are being paid to develop new ones with better and more effective proapoptotic potential. Nevertheless, despite recent developments in this field, there are still numerous malignancies showing a varying degree of resistance to cell death due to the corrupted signaling pathways and genetic alterations, often in conjunction with expansive proliferation rate. It has been shown that topoisomerase inhibiting agents such as etoposide, camptothecin and others represent a powerful and dynamic group of cytostatic chemicals used in experimental and clinical conditions. So, it is a group of microtubule targeting poisons comprising classical colchicines on the one hand and new taxanes on the other hand. Since several members of both groups have been evidenced as apoptosis inducers operating via distinct mechanism, their combination should theoretically enhance the final therapeutic outcome. This minireview focuses on the possibilities of such a combinational approach with respect to possible benefits and hazards of this strategy.