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Orthotopic Transplantation of Breast Tumors as Preclinical Models for Breast Cancer
Published on: May 18, 2020
Multidrug resistance in breast cancer: from in vitro models to clinical studies
1Academic Unit of Clinical Oncology, DU10, Medical School, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK. n.wind@sheffield.ac.uk
Abstract:
The development of multidrug resistance (MDR) and subsequent relapse on therapy is a widespread problem in breast cancer, but our understanding of the underlying molecular mechanisms is incomplete. Numerous studies have aimed to establish the role of drug transporter pumps in MDR and to link their expression to response to chemotherapy. The ATP-binding cassette (ABC) transporters are central to breast cancer MDR, and increases in ABC expression levels have been shown to correlate with decreases in response to various chemotherapy drugs and a reduction in overall survival. But as there is a large degree of redundancy between different ABC transporters, this correlation has not been seen in all studies. This paper provides an introduction to the key molecules associated with breast cancer MDR and summarises evidence of their potential roles reported from model systems and clinical studies. We provide possible explanations for why despite several decades of research, the precise role of ABC transporters in breast cancer MDR remains elusive.
Insights
Multidrug resistance (MDR) in breast cancer is a major challenge. While ATP-binding cassette (ABC) transporters are implicated, their exact role in MDR remains unclear due to transporter redundancy.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Multidrug resistance (MDR) and treatment relapse are significant problems in breast cancer management.
- The molecular mechanisms driving MDR in breast cancer are not fully understood.
- ATP-binding cassette (ABC) transporters are frequently investigated for their role in MDR.
Purpose of the Study:
- To introduce key molecules involved in breast cancer MDR.
- To summarize evidence on the role of ABC transporters in breast cancer MDR from model systems and clinical studies.
- To explore reasons for the elusive role of ABC transporters in breast cancer MDR.
Main Methods:
- Literature review of model systems and clinical studies.
- Analysis of existing research on ABC transporters and breast cancer MDR.
- Synthesis of evidence regarding the correlation between ABC transporter expression and chemotherapy response.
Main Results:
- Increased expression of ATP-binding cassette (ABC) transporters often correlates with reduced chemotherapy response and overall survival in breast cancer.
- However, significant redundancy among different ABC transporters can obscure this correlation in some studies.
- Evidence from various studies suggests a complex, multifaceted role for ABC transporters in breast cancer MDR.
Conclusions:
- Despite extensive research, the precise contribution of ABC transporters to breast cancer MDR remains elusive.
- Understanding the complex interplay and redundancy of ABC transporters is crucial for overcoming MDR.
- Further research is needed to fully elucidate the role of these transporters in treatment failure and to develop effective therapeutic strategies.
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