P-glycoprotein Expression in Solid Tumors – An Analysis

Abstract

P-glycoprotein is an efflux transporter belonging to the ATP Binding Cassette (ABC) family of transporters and is encoded by Multidrug resistance (MDR1) gene. It is primarily involved in efflux of xenobiotics that permeate the external boundaries into the tissues. Chemotherapeutics are target oriented drugs for destruction of malgrowing cells to combat critical illness (viz., cancer, AIDS, malaria, tuberculosis, etc.) which are thus interpreted as harmful by the MDR system. This might cause overexpression of p-glycoprotein in such organs. Overexpression of p-glycoprotein rather than up-regulation of ABC-transporters are associated with resistance of tumours to multiple chemotherapeutic agents, thus reducing their bioavailability in the specific organs. The present review thus attempts to coalesce this expression data in solid tumors which maybe intrinsic to the organ or an after-effect of chemotherapy, thus altering the pharmacodynamics of drug permeation. For this purpose, peer reviewed publications have been analysed to delineate the range of fluctuation in p-glycoprotein expression in different organs after therapeutic intervention. It is extensively distributed and highly overexpressed in all neural tumors, reproductive and genito-urinary cancer, sarcomas, oral squamous cell carcinoma, NSCLC, hepatocellular carcinoma, cholangiocarcinoma, pancreatic tumor, etc. On the other hand, p-glycoprotein expression in cancer of the larynx, small cell lung carcinoma (SCLC), osteosarcoma, rhabdosarcoma, often show substantial decrease in expression, though not in all studies. There was no consistent increase or decrease in p-glycoprotein expression in all the tumors.