Open AccessMechanisms of doxorubicin resistance in hepatocellular carcinoma
Author(s) -
Josiah Cox,
Steven A. Weinman
Publication year - 2016
Publication title -
hepatic oncology
Language(s) - English
Resource type - Journals
eISSN - 2045-0931
pISSN - 2045-0923
DOI - 10.2217/hep.15.41
Subject(s) - doxorubicin , hepatocellular carcinoma , medicine , cancer research , multiple drug resistance , drug resistance , efflux , chemotherapy , topoisomerase , cancer , pharmacology , biology , in vitro , biochemistry , genetics , microbiology and biotechnology
Hepatocellular carcinoma, one of the most common solid tumors worldwide, is poorly responsive to available chemotherapeutic approaches. While systemic chemotherapy is of limited benefit, intra-arterial delivery of doxorubicin to the tumor frequently produces tumor shrinkage. Its utility is limited, in part, by the frequent emergence of doxorubicin resistance. The mechanisms of this resistance include increased expression of multidrug resistance efflux pumps, alterations of the drug target, topoisomerase, and modulation of programmed cell death pathways. Many of these effects result from changes in miRNA expression and are particularly prominent in tumor cells with a stem cell phenotype. This review will summarize the current knowledge on the mechanisms of doxorubicin resistance of hepatocellular carcinoma and the potential for approaches toward therapeutic chemosensitization.