engleski

Molecular mechanisms of cell sensitivity/resistance to anti-cancer drugs

Cell exposure to cytotoxic drugs can cause diverse harmful effects. As maintenance of genomic stability is essential for the survival of organisms, during the evolution the cells have developed numerous strictly regulated pathways to minimize these effects. The events that influence cell response can be principally divided in two groups: those that occur upstream of remained DNA damage, or downstream of it. Generally, the first group involves cell adhesion and downstream protective mechanisms, such as altered intracellular drug-accumulation, activation of detoxification system, efficient DNA damage repair, etc., while the second involves the induction of programmed cell death. Each of these events is potentially of crucial importance in cell response to cytotoxic drugs, and is strongly dependent on cell status. The mechanisms that contribute to drug resistance have been examined extensively as well. However, for the endpoint of cytotoxicity, our knowledge is still quite fragmented because cell dies due to complex network of signalling pathways that become activated upon exposure to harmful compounds. In the last fifteen years we have developed a several sublines of tumor cells resistant to widely used anti-cancer drugs, and determined several mechanisms that contribute to drug-resistance. These results will be presented in the lecture as well.

drug resistance; glutathione; programmed cell death; cell adhesion

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