MULTIDRUG-RESISTANCE IN MALIGNANCIES OF CHILDREN

Purpose. Increased expression of P-glycoprotein has been shown to be t he molecular cause of multidrug resistance in tumor cell lines in vitr o. Sensitive immunohistochemical and molecular biological techniques h ave been developed to detect the presence of P-glycoprotein in clinica l samples of tumors. This review examines the current evidence for a c linically relevant role of P-glycoprotein and strategies to overcome m ultidrug resistance. Design. Chemotherapy plays an important role in c uring many malignancies. However, treatment still fails in a proportio n of patients. Since many of the chemotherapeutic drugs used are subst rates of the P-glycoprotein efflux transporter, these malignancies are good models for the study of clinical multidrug resistance. Results. A strong association has been observed between the expression of P-gly coprotein and results of treatment of neuroblastoma and rhabdomyosarco ma in children and acute myelogenous leukemia, lymphoma and myeloma in adults. Conversely, although carcinomas often overexpress P-glycoprot ein constitutively, whether a multidrug resistance mechanism is the ra te-limiting factor in response to chemotherapy has not been establishe d. Several clinical trials have been initiated to determine whether ph armacologic chemosensitization improves the outcome of chemotherapy-tr eated malignancies. Conclusion. The clinical relevance of the P-glycop rotein drug efflux mechanism may ultimately be confirmed by the succes sful prevention of chemotherapy failure with the use of chemosensitize rs.