Key points are not available for this paper at this time.
The Journal of the National Cancer Institute published our paper entitled “Expression of a Multidrug Resistance Gene in Human Cancers” ( 1 ) 26 years ago. It was the first systematic determination of whether the energy-dependent multidrug efflux pump P-glycoprotein (P-gp), the product of the ABCB1 (MDR1) gene, was expressed in human cancers and has been cited over 1200 times. Four hundred cancers were studied, and the conclusion was that expression was widespread both in intrinsically drug-resistant cancers such as colon, pancreatic, liver, adrenocortical, and kidney cancers, and in some cancers that acquired resistance, such as leukemias, lymphomas, breast cancer, and neuroblastoma. Other cancers at the time of initial presentation, such as lung cancers (except for neuroendocrine tumors), ovarian cancer, esophageal cancer, and mesothelioma expressed little or no P-glycoprotein. The major conclusions of this paper, which have withstood the test of time (see below) were: 1) that P-gp was expressed at levels sufficient to confer drug resistance in many different difficult-to-treat cancers, 2) that its expression appeared during the acquisition of resistance for some cancers, indicating a possible role for P-gp in acquired resistance, 3) that many cancers did not appear to express P-gp mRNA at detectable levels and therefore efforts to inhibit P-gp and reverse resistance in these cancers were unlikely to succeed, and 4) that it remained to be proven whether P-gp expression, though perhaps sufficient for drug resistance in cancers, was the main cause of resistance in any cancer. Considerable effort has been devoted to answer this last question: Are P-gp or other multidrug transporters discovered since (see below) useful targets for drug development with the possible outcome of reversing multidrug resistance in cancer?
Gottesman et al. (Tue,) studied this question.