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Cancers 2015, 7(4), 2063-2082; doi:10.3390/cancers7040877

Development, Maintenance, and Reversal of Multiple Drug Resistance: At the Crossroads of TFPI1, ABC Transporters, and HIF1

1
Department of Medicine, University of Saskatchewan, Saskatoon, SK S7N 0W8, Canada
2
Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, SK S7N 0W8, Canada
*
Author to whom correspondence should be addressed.
Academic Editors: Zhe-Sheng (Jason) Chen and Dong-Hua (Hana) Yang
Received: 11 September 2015 / Accepted: 10 October 2015 / Published: 16 October 2015
(This article belongs to the Special Issue Drug/Radiation Resistance in Cancer Therapy)
View Full-Text   |   Download PDF [834 KB, uploaded 16 October 2015]   |  

Abstract

Early detection and improved therapies for many cancers are enhancing survival rates. Although many cytotoxic therapies are approved for aggressive or metastatic cancer; response rates are low and acquisition of de novo resistance is virtually universal. For decades; chemotherapeutic treatments for cancer have included anthracyclines such as Doxorubicin (DOX); and its use in aggressive tumors appears to remain a viable option; but drug resistance arises against DOX; as for all other classes of compounds. Our recent work suggests the anticoagulant protein Tissue Factor Pathway Inhibitor 1α (TFPI1α) plays a role in driving the development of multiple drug resistance (MDR); but not maintenance; of the MDR state. Other factors; such as the ABC transporter drug efflux pumps MDR-1/P-gp (ABCB1) and BCRP (ABCG2); are required for MDR maintenance; as well as development. The patient population struggling with therapeutic resistance specifically requires novel treatment options to resensitize these tumor cells to therapy. In this review we discuss the development, maintenance, and reversal of MDR as three distinct phases of cancer biology. Possible means to exploit these stages to reverse MDR will be explored. Early molecular detection of MDRcancers before clinical failure has the potential to offer new approaches to fighting MDRcancer. View Full-Text
Keywords: multiple drug resistance/MDR; TFPI; hypoxia; HIF1; breast cancer multiple drug resistance/MDR; TFPI; hypoxia; HIF1; breast cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Arnason, T.; Harkness, T. Development, Maintenance, and Reversal of Multiple Drug Resistance: At the Crossroads of TFPI1, ABC Transporters, and HIF1. Cancers 2015, 7, 2063-2082.

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