THE ROLE OF MDR-1 IN REFRACTORY LYMPHOMA

Although lymphoma is one of the few solid tumours for which chemothera py can be curative, the treatment of refractory lymphoma remains a maj or clinical problem. P-glycoprotein (Pgp), the drug efflux pump encode d by the MDR-1 gene is associated with multidrug resistance in several laboratory models of drug resistance, and a number of investigators h ave attempted to establish a role for Pgp in refractory lymphoma. Desp ite a considerable variability in the results of these studies investi gating Pgp expression in lymphoma, the preponderance of the data sugge sts that Pgp may at least in part account for drug resistance in this disease. Several clinical trials using Pgp modulating compounds have a ttempted to reverse the drug resistant phenotype of refractory lymphom a. These studies, although difficult to interpret because of the effec t of Pgp modulators on chemotherapeutic drug pharmacokinetics, also su ggest a role for Pgp in mediating drug resistance in a subset of patie nts with refractory lymphoma. Studies with newer Pgp modulating agents with phase III designs will be needed before Pgp modulation can be co nsidered for incorporation into routine oncologic practice.