{"title":"Mechanisms of doxorubicin resistance in hepatocellular carcinoma.","authors":"Josiah Cox, S. Weinman","doi":"10.2217/HEP.15.41","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":44854,"journal":{"name":"Hepatic Oncology","volume":"3 1 1","pages":"57-59"},"PeriodicalIF":1.2000,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/HEP.15.41","citationCount":"116","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hepatic Oncology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2217/HEP.15.41","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 116
Abstract
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.
期刊介绍:
Primary liver cancer is the sixth most common cancer in the world, and the third most common cause of death from malignant disease. Traditionally more common in developing countries, hepatocellular carcinoma is becoming increasingly prevalent in the Western world, primarily due to an increase in hepatitis C virus infection. Emerging risk factors, such as non-alcoholic fatty liver disease and obesity are also of concern for the future. In addition, metastatic tumors of the liver are more common than primary disease. Some studies report hepatic metastases in as many as 40 to 50% of adult patients with extrahepatic primary tumors. Hepatic Oncology publishes original research studies and reviews addressing preventive, diagnostic and therapeutic approaches to all types of cancer of the liver, in both the adult and pediatric populations. The journal also highlights significant advances in basic and translational research, and places them in context for future therapy. Hepatic Oncology provides a forum to report and debate all aspects of cancer of the liver and bile ducts. The journal publishes original research studies, full reviews and commentaries, with all articles subject to independent review by a minimum of three independent experts. Unsolicited article proposals are welcomed and authors are required to comply fully with the journal''s Disclosure & Conflict of Interest Policy as well as major publishing guidelines, including ICMJE and GPP3.