New trends for overcoming ABCG2/BCRP-mediated resistance to cancer therapies
1Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY, 14263, USA. david.westover@roswellpark.org.
Abstract:
ATP-binding cassette (ABC) transporters make up a superfamily of transmembrane proteins that play a critical role in the development of drug resistance. This phenomenon is especially important in oncology, where superfamily member ABCG2 (also called BCRP - breast cancer resistance protein) is known to interact with dozens of anti-cancer agents that are ABCG2 substrates. In addition to the well-studied and well-reviewed list of cytotoxic and targeted agents that are substrates for the ABCG2 transporter, a growing body of work links ABCG2 to multiple photodynamic therapy (PDT) agents, and there is a limited body of evidence suggesting that ABCG2 may also play a role in resistance to radiation therapy. In addition, the focus of ABC transporter research in regards to therapeutic development has begun to shift in the past few years. The shift has been away from using pump inhibitors for reversing resistance, toward the development of therapeutic agents that are poor substrates for these efflux pump proteins. This approach may result in the development of drug regimens that circumvent ABC transporter-mediated resistance entirely. Here, it is our intention to review: 1) recent discoveries that further characterize the role of ABCG2 in oncology, and 2) advances in reversing and circumventing ABC transporter-mediated resistance to anti-cancer therapies.
Insights
ATP-binding cassette (ABC) transporters, like ABCG2, drive cancer drug resistance. New strategies focus on developing therapies that bypass ABCG2, rather than inhibiting it, to overcome resistance in oncology.
Area of Science:
- Molecular Biology
- Oncology
- Pharmacology
Background:
- ATP-binding cassette (ABC) transporters are transmembrane proteins crucial in drug resistance, particularly in oncology.
- ABCG2 (breast cancer resistance protein) is a key transporter interacting with numerous anti-cancer drugs, including cytotoxic and targeted agents.
- Emerging evidence links ABCG2 to resistance against photodynamic therapy (PDT) and radiation therapy.
Purpose of the Study:
- To review recent discoveries on the role of ABCG2 in oncology.
- To examine advances in reversing and circumventing ABC transporter-mediated resistance to anti-cancer therapies.
- To highlight a shift in therapeutic development away from pump inhibitors towards agents that are poor ABCG2 substrates.
Main Methods:
- Literature review of recent discoveries in ABCG2 function and oncology.
- Analysis of therapeutic strategies for overcoming ABC transporter-mediated resistance.
- Synthesis of evidence linking ABCG2 to PDT and radiation therapy resistance.
Main Results:
- ABCG2 significantly contributes to resistance against various anti-cancer agents, including novel classes like PDT agents.
- A paradigm shift is occurring in therapeutic development, focusing on circumventing ABC transporter activity.
- Developing anti-cancer agents that are poor substrates for ABCG2 offers a promising approach to overcome resistance.
Conclusions:
- Understanding ABCG2's multifaceted role in oncology is essential for effective cancer treatment.
- Novel therapeutic strategies are emerging to combat ABC transporter-mediated drug resistance.
- Future research should focus on developing drug regimens that bypass ABCG2 efflux to improve patient outcomes.
More Related Videos
08:46Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
09:38Establishing Dual Resistance to EGFR-TKI and MET-TKI in Lung Adenocarcinoma Cells In Vitro with a 2-step Dose-escalation Procedure
Published on: August 11, 2017
Related Concept Videos
02:56Treatment Resistant Cancers
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:56Treatment Resistent Cancers
02:38Mitogens and the Cell Cycle
01:27Tumor Immunotherapy