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Front. Pharmacol., 11 February 2013 | http://dx.doi.org/10.3389/fphar.2013.00010

The molecular chaperone GRP78/BiP in the development of chemoresistance: mechanism and possible treatment

  • Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany

Treatment of several types of cancer such as lung, breast, prostate, and pancreas has shown notable progresses in the past decades. However, after an initial response, tumors eventually became resistant to chemotherapy. This phenomenon, known as chemoresistance, accounts for the death of most cancer patients. Several studies in patients refractory to therapy have revealed the upregulation of the molecular chaperone GRP78/Binding Protein, BiP (BiP) both at the RNA and protein expression level. Furthermore GRP78/BiP relocates to the cell membrane in malignant but not in benign cells. In this communication we review studies on the role and the mechanism of action of GRP78/BiP during development of chemoresistance in cancer cells. In addition we discuss the possible role of GRP78 as a biomarker and as a target in cancer therapy.

Keywords: cell stress, chaperone, unfolded protein response, drug resistance, therapy

Citation: Roller C and Maddalo D (2013) The molecular chaperone GRP78/BiP in the development of chemoresistance: mechanism and possible treatment. Front. Pharmacol. 4:10. doi: 10.3389/fphar.2013.00010

Received: 14 December 2012; Paper pending published: 02 January 2013;
Accepted: 21 January 2013; Published online: 11 February 2013.

Edited by:

Gerald Batist, McGill University, Canada

Reviewed by:

Marc Poirot, Institut National de la Santé et de la Recherche Médicale, France
Jian Hui Wu, McGill University, Canada

Copyright: © 2013 Roller and Maddalo. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: Danilo Maddalo, Institute of Toxicology and Genetics, Karlsruhe Institute of Technology, Hermann von Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany. e-mail: danilo.maddalo@kit.edu