Summary:
Resistance to cytotoxic drugs is a serious drawback in the treatment of patients with tumours, both of the
haemopoietic and non-haemopoietic origin. The cytotoxic effect of drugs on the malignant cells manifests as the
process of apoptosis. In the resistant malignant cells, apoptosis becomes prevented by several mechanisms. The
multidrug resistance (MDR) is one of the principal mechanisms when the cancer cells develop resistance to multiple
chemically and functionally unrelated cytotoxic compounds. The decrease of the cytotoxic drug concentration at the
molecular target site may come from activation of some efflux membrane systems participating in the transport of
cytotoxic drugs out of the cell (e.g. Pgp, MDR, and LRP). Another mechanism of resistance is the increased enzymatic
detoxification of the drug by glutathion-s-transferase system. Changes in the molecular target of the cytotoxic drug
such as topoisomerase molecule can be also responsible for the resistance. At least two additional mechanisms of
resistance of tumour cells were identified. Resistance can come from either deregulation of proapoptotic mechanisms
in tumour cells or by increased activity of reparation processes which control the damaged molecule of DNA. Several
methods that detect the cause of resistance in distinct cell populations have been developed. The great effort is now
focused on both the detection of mechanisms of the resistance and on the clinical procedures of overcoming the
resistance to cytotoxic drugs.
Key words:
multidrug resistance, apoptosis, efflux systems, topoisomerase, cell cycle, DNA reparation, flow
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