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Plasma Membrane Transporters as Biomarkers and Molecular Targets in Cholangiocarcinoma

Jose J G Marin1, Rocio I R Macias1, Candela Cives-Losada1

  • 1HEVEFARM Group, Center for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Carlos III National Institute of Health. University of Salamanca, IBSAL, 37007-Salamanca, Spain.

Cells
|February 27, 2020
PubMed

Insights

Cholangiocarcinoma (CCA) liver cancer is resistant to chemotherapy due to impaired drug transport. Targeting solute carrier (SLC) and ATP-binding cassette (ABC) transporters offers new strategies to overcome multidrug resistance (MDR) in CCA.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Advanced cholangiocarcinoma (CCA) exhibits extreme resistance to chemotherapy, contributing to poor patient prognosis.
  • Chemoresistance mechanisms in CCA involve impaired drug uptake via solute carrier (SLC) proteins and active drug export by ATP-binding cassette (ABC) proteins.
  • These transport processes reduce intracellular concentrations of chemotherapeutic agents, limiting their efficacy.

Purpose of the Study:

  • To explore the role of the cancer transportome in CCA chemoresistance.
  • To evaluate plasma membrane transporters as potential therapeutic targets for sensitizing CCA to chemotherapy.
  • To assess the utility of differentially expressed transporters as diagnostic and prognostic biomarkers in CCA.

Main Methods:

  • Analysis of the cancer transportome, focusing on solute carrier (SLC) and ATP-binding cassette (ABC) proteins.
  • Investigation of mechanisms regulating drug uptake and export in CCA cells.
  • Evaluation of transporter expression patterns for potential biomarker applications.

Main Results:

  • The cancer transportome, comprising SLC and ABC proteins, is crucial in defining the multidrug resistance (MDR) phenotype of CCA cells.
  • Modulating the expression or function of SLC and ABC transporters presents a strategy to enhance chemotherapy sensitivity.
  • Certain transporters are differentially expressed in CCA, suggesting their potential as diagnostic or prognostic markers.

Conclusions:

  • Targeting the cancer transportome, specifically SLC and ABC transporters, is a promising approach to overcome chemotherapy resistance in cholangiocarcinoma.
  • Understanding transporter roles can lead to novel therapeutic strategies and improved diagnostic/prognostic tools for CCA patients.
Keywords:
ABC proteinsSLC proteinsbiliary cancerchemoresistancechemosensitivitychemotherapyhepatocellular carcinomatransporteruptake

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