Human ABC transporter ABCG2 in cancer chemotherapy: drug molecular design to circumvent multidrug resistance

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Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
08:59

Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down

Published on: December 11, 2017

Toshihisa Ishikawa1, Hikaru Saito, Hiroyuki Hirano

  • 1Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Japan. Toshi-i@gsc.riken.jp

Methods in Molecular Biology (Clifton, N.J.)
|July 24, 2012
PubMed

Insights

Human ATP-binding cassette (ABC) transporter ABCG2, also known as BCRP, is key in cancer multidrug resistance. Researchers developed a high-speed screening method and QSAR algorithm to understand ABCG2-drug interactions and design new cancer therapies.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • The ATP-binding cassette (ABC) transporter ABCG2 (BCRP) plays a crucial role in multidrug resistance (MDR) in human cancers.
  • ABCG2 exhibits broad substrate specificity, transporting structurally diverse compounds, similar to other ABC transporters like ABCB1, ABCC1, and ABCC2.

Purpose of the Study:

  • To investigate the relationship between molecular structure and ABCG2-mediated transport activity.
  • To develop strategies for circumventing cancer multidrug resistance through mechanism-based molecular design.

Main Methods:

  • Development of a high-speed screening method to analyze ABCG2 substrate specificity.
  • Application of a quantitative structure-activity relationship (QSAR) algorithm to evaluate ABCG2-drug interactions.

Main Results:

  • A novel high-throughput screening method was established for assessing ABCG2 transporter activity.
  • A QSAR model was developed to predict and understand interactions between drugs and ABCG2.

Conclusions:

  • The developed methods provide insight into ABCG2 substrate specificity and drug interactions.
  • This research facilitates transport mechanism-based molecular design to overcome cancer multidrug resistance.

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