Drug resistance in the treatment of sarcomas

The antineoplastic action and development of drug resistance are reviewed for chemotherapeutic agents used in the treatment of sarcoma, including alkylating agents (cyclophosphamide, ifosphamide, dacarbazine), platinum compounds (cisplatin, carboplatin), the anthracycline compound doxorubicin, the topoisomerase II inhibitor etoposide, and the taxanes (paclitaxel, taxotere). Drug resistance mechanisms discussed include changes in intracellular glutathione and metallothione levels, increased aldehyde dehydrogenase levels, enhanced DNA repair and protection from apoptosis (for alkylating agents); increased 0-6 alkyltranferase levels (for dacarbazine); multidrug resistance 1- and multidrug resistance associated protein-mediated drug export from cells (anthracyclines, taxanes); and structural alteration of microtubules (taxanes).