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

Curr Med Chem. 2019;26(7):1224-1250. doi: 10.2174/0929867325666180105103637.

Abstract

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.

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

Publication types

  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism*
  • Carcinoma, Hepatocellular / metabolism*
  • Colorectal Neoplasms / metabolism*
  • Drug Resistance, Multiple / drug effects*
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Liver Neoplasms / metabolism*
  • Multidrug Resistance-Associated Protein 2

Substances

  • ABCC2 protein, human
  • ATP-Binding Cassette Transporters
  • Multidrug Resistance-Associated Protein 2