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ABC Transporter-Mediated Multidrug-Resistant Cancer

Haneen Amawi1, Hong-May Sim2, Amit K Tiwari3

  • 1Department of Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, Irbid, Jordan.

Advances in Experimental Medicine and Biology
|October 2, 2019
PubMed

Insights

ATP-binding cassette (ABC) transporters influence drug pharmacokinetics and are key in multidrug resistance (MDR). This review details their roles in disease and cancer, focusing on overcoming MDR with therapeutic strategies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • ATP-binding cassette (ABC) transporters actively transport diverse substrates across cellular membranes.
  • These transporters significantly impact drug pharmacokinetics and xenobiotic metabolism.
  • Dysregulation of ABC transporters is implicated in human disease pathogenesis and cancer multidrug resistance (MDR).

Purpose of the Study:

  • To review the localization and physiological roles of ABC transporters in the human body.
  • To elucidate the involvement of ABC transporters in the development of multidrug resistance (MDR).
  • To discuss therapeutic strategies targeting ABC transporters for overcoming MDR and analyze the efficacy of inhibitors.

Main Methods:

  • Literature review of ABC transporter functions.
  • Detailed examination of specific transporters: P-glycoprotein (P-GP), multidrug resistance-associated proteins (MRPs), and breast cancer resistance protein (BCRP/ABCG2).
  • Analysis of therapeutic targets and strategies for MDR reversal.

Main Results:

  • ABC transporters are crucial for cellular membrane transport, affecting drug disposition.
  • Overexpression of ABC transporters in cancer cells contributes to chemotherapeutic resistance.
  • Specific transporters like P-GP, MRPs, and BCRP are central to MDR mechanisms.

Conclusions:

  • Understanding ABC transporter roles is vital for disease and cancer therapy.
  • Targeting ABC transporters offers potential strategies to overcome MDR.
  • Challenges and explanations for the limited efficacy of current ABC transporter inhibitors require further investigation.
Keywords:
ABC transportersBreast cancer resistance proteinMultidrug resistanceMultidrug resistance-associated proteinP-glycoprotein

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