4.6 Review

ABC Transporters: Regulation and Association with Multidrug Resistance in Hepatocellular Carcinoma and Colorectal Carcinoma

Journal

CURRENT MEDICINAL CHEMISTRY
Volume 26, Issue 7, Pages 1224-1250

Publisher

BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867325666180105103637

Keywords

ABCB1; ABCC2; ABCG2; chemotherapy; hepatocellular carcinoma; colorectal carcinoma; multidrug resistance; transcriptional regulation

Funding

  1. Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET) [PIP 2016-0202]
  2. Fondo para la Investigacion Cientifica y Tecnologica (FONCyT) [PICT 2015-1358, PICT 2013-1503, PICT 2014-2596, PICT 2015-0836]
  3. German Research Foundation (DFG) [RI2673/1-1]

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For most cancers, the treatment of choice is still chemotherapy despite its severe adverse effects, systemic toxicity and limited efficacy due to the development of multidrug resistance (MDR). MDR leads to chemotherapy failure generally associated with a decrease in drug concentration inside cancer cells, frequently due to the overexpression of ABC transporters such as P-glycoprotein (P-gp/MDR1/ABCB1), multidrug resistance-associated proteins (MRPs/ABCCs), and breast cancer resistance protein (BCRP'ABCG2), which limits the efficacy of chemotherapeutic drugs. The aim of this review is to compile information about transcriptional and post-transcriptional regulation of ABC transporters and discuss their role in mediating MDR in cancer cells. This review also focuses on drug resistance by ABC efflux transporters in cancer cells, particularly hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) cells. Some aspects of the chemotherapy failure and future directions to overcome this problem are also discussed.

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