Ways for Overcoming Drug Resistance in Cancer: Designing New Drugs: Invited Commentary

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Aksoy Y.

TURKIYE KLINIKLERI TIP BILIMLERI DERGISI, vol.30, no.6, pp.2011-2016, 2010 (SCI-Expanded) identifier identifier


Drug resistance in cancer treatment is one of the causes hindering success. Thus increasing the effectiveness of current drugs or designing new drugs are being tried. Two mechanisms are hold to account for drug resistance in tumor cells. One of these is the interaction between efflux transporter protein and Phase II conjugation enzymes. It is especially emphasized that glutathion S-transferase enzyme and efflux pumps are overexpressed in tumor cells and thereby reactivity of anticancer dugs are reported to decrease. Another mechanism that have gained importance in recent years is exhibition of glutathion S-transferases' playing role in control of signal proteins taking part in programmed cell death. In many cancer types, level of glutathion S-transferase is observed to increase with entry of chemotherapeutics into the cell. Apoptosis is emphasized to interrupt with overexpression of the enzyme. It was put forward that some proteins that are responsible for signal transmission in apoptotic cycle have been repressed by glutatihon S-transferase and accordingly cancer cell survived. The complex generated by the enzyme needs to be cleared away by c-jun NH2-terminal kinase (INK) that is one of the proteins taking part in signal transmission. Thus glutathion S-transferase enzyme have been the focus of pharmaceutical researches for increasing the effectiveness of anti-cancer drugs recently and inhibitors with distinct properties have begun to be produced. Researches are maintained in vivo and in vitro. Outcomes of studies conducted for many cancer types are encouraging for abolishing drug resistance. This review aims to provide a general information about GST inhibitors produced for providing the tumor cells' to enter apoptotic pathway and consequently for breaking drug resistance and their mechanisms of action. In the light of obtained data, GST seems to be the new target in designing original drugs for cancer treatment.