Targeting breast cancer resistance protein (BCRP/ABCG2): Functional inhibitors and expression modulators

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Multidrug resistance (MDR) is a primary cause of cancer therapy failure, frequently mediated by ATP-binding cassette (ABC) transporters.
• Breast cancer resistance protein (BCRP), also known as ABCG2, is a key ABC transporter implicated in MDR across various cancers.
• Overcoming BCRP-mediated MDR is crucial for improving cancer treatment outcomes.

Purpose of the Study:

• To provide a comprehensive overview of identified inhibitors targeting ABCG2.
• To discuss chemical properties and experimental methodologies for characterizing ABCG2 inhibitors.
• To explore the potential of ABCG2 inhibitors in targeting cancer stem cells (CSCs) and enhancing therapeutic responses.

Main Methods:

• Literature review of identified ABCG2 inhibitors.
• Analysis of chemical aspects and experimental characterization methods for inhibitors.
• Discussion of biological requirements for preclinical testing and mechanisms of action.

Main Results:

• Numerous compounds targeting ABCG2 have been discovered.
• Various experimental approaches are employed to identify and characterize ABCG2 inhibitors.
• Potential strategies for modulating ABCG2 at transcriptional and protein levels are discussed.

Conclusions:

• Inhibitors of ABCG2 represent a promising strategy to combat MDR in cancer.
• Targeting ABCG2, especially in CSCs, may improve treatment efficacy and response rates.
• Further research into ABCG2 modulators is warranted for clinical translation.