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.