ABSTRACT
Cancer is the second leading cause of death in developed countries, exceeded only by heart disease. About half a million people die of cancer every year in the USA alone, that is more than 1,500 people a day. Chemotherapy is a major weapon in our fight against malignant diseases. Still, in numerous cases even combination chemotherapy is ineffective: the tumor cells may first respond but in a relapse become resistant to multiple agents. There are several forms of cancer drug resistance, based on the activation of specific drug metabolizing enzymes or defense mechanisms, protecting the cellular targets of anticancer drug action. These include, e.g., decreased levels and/or mutations in the topoisomerase protein, enhanced DNA repair, increased activity of dehydrofolate reductase, reduced methotrexate influx, or even a combination of mechanisms, preventing drug-induced apoptosis of the tumor cells.
