ABC transporters in breast cancer: their roles in multidrug resistance and beyond

J Drug Target. 2022 Nov;30(9):927-947. doi: 10.1080/1061186X.2022.2091578. Epub 2022 Jun 26.

Abstract

ATP-binding cassette (ABC) transporters are membrane-spanning proteins involved in cholesterol homeostasis, transport of various molecules in and out of cells and organelles, oxidative stress, immune recognition, and drug efflux. They are long implicated in the development of multidrug resistance in cancer chemotherapy. Existing clinical and molecular evidence has also linked ABC transporters with cancer pathogenesis, prognostics, and therapy. In this review, we aim to provide a comprehensive update on all ABC transporters and their roles in drug resistance in breast cancer (BC). For solid tumours such as BC, various ABC transporters are highly expressed in less differentiated subtypes and metastases. ABCA1, ABCB1 and ABCG2 are key players in BC chemoresistance. Restraining these transporters has evolved as a possible mechanism to reverse this phenomenon. Further, ABCB1 and ABCC1 are important in BC prognosis. Newer therapeutic approaches have been developed to target all these molecules to dysregulate their effect, reduce cell viability, induce apoptosis, and increase drug sensitivity. In the future, targeted therapy for specific genetic variations and upstream or downstream molecules can help improve patient prognosis.

Keywords: ABC transporter; breast cancer; chemoresistance; lncRNA; miRNA; polymorphism.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters* / genetics
  • ATP-Binding Cassette Transporters* / metabolism
  • ATP-Binding Cassette Transporters* / pharmacology
  • Adenosine Triphosphate
  • Breast Neoplasms* / metabolism
  • Cholesterol
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins

Substances

  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • Adenosine Triphosphate
  • Cholesterol