Role of transportome in the pharmacogenomics of hepatocellular carcinoma and hepatobiliary cancer

Pharmacogenomics. 2019 Aug;20(13):957-970. doi: 10.2217/pgs-2019-0033.

Abstract

An important factor determining the pharmacological response to antitumor drugs is their concentrations in cancer cells, which accounts for the net interaction with their intracellular molecular targets. Accordingly, mechanisms leading to reduced intracellular levels of active agents play a crucial role in cancer chemoresistance. These include impaired drug uptake through solute carrier (SLC) proteins and efficient drug export by ATP-dependent pumps belonging to the ATP-binding cassette (ABC) superfamily of proteins. Since the net movement of drugs in-and-out the cells depends on the overall expression of carrier proteins, defining the so-called transportome, special attention has been devoted to the study of transcriptome regarding these proteins. Nevertheless, genetic variants affecting SLC and ABC genes may markedly affect the bioavailability and, hence, the efficacy of anticancer drugs.

Keywords: chemoresistance; chemotherapy; liver cancer; mutation; transportome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biological Transport / drug effects
  • Biological Transport / genetics
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / genetics*
  • Digestive System Diseases / drug therapy
  • Digestive System Diseases / genetics*
  • Drug Resistance, Neoplasm / drug effects
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / genetics*
  • Pharmacogenetics / methods

Substances

  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents