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Glutathione transferases and development of new principles to overcome drug resistance
Authors:Andrea Sau  Francesco Valentino  Anna Maria Caccuri
Institution:a Department of Chemical Sciences and Technologies, University of “Tor Vergata”, Rome, Italy
b Department of Internal Medicine, University of “Tor Vergata”, Rome, Italy
c Children’s Hospital, Istituto di Ricovero e Cura a Carattere Scientifico “Bambin Gesù”, Rome, Italy
Abstract:Chemoresistance is a multifactorial phenomenon and many studies clearly show that a coordinated expression of efflux transporter proteins and phase II conjugating enzymes in tumor cells is linked to the development of the multidrug resistance phenotype. In particular, the overexpression of glutathione S-transferases and efflux pumps in tumors may reduce the reactivity of various anticancer drugs. In recent years it has become evident that glutathione S-transferases are also involved in the control of apoptosis through the inhibition of the JNK signaling pathway. As such, the glutathione S-transferase superfamily has become the focus of extensive pharmaceutical research in attempt to generate more efficient anticancer agents. Here we present an overview of the GST inhibitors and the GST-activated pro-drugs utilized to date to overcome drug resistance.
Keywords:GST  MDR  MAPK  Pro-drug  Inhibitor
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