Breast Cancer

What we do

Patterns of gene expression direct cell fate, including proliferation and differentiation, which define organismal development and tissue characteristics. Transcription factors regulate gene expression and their activities are frequently deregulated in cancer. We are investigating the transcriptional processes that control breast cancer development and progression, to develop new breast cancer treatments and improve outcome. 

Why it is important

The estrogen receptor (ER) is the key transcriptional driver of breast cancer development and progression in 80% of cases and is the target for endocrine therapies that block ER activity. Unfortunately, many patients become resistant to these therapies, highlighting the need for improved understanding of the mechanisms by which ER control breast cancer progression.

How it can benefit patients

By understanding mechanisms of ER action in endocrine responsive and resistant breast cancer, we aim to improve patient outcomes through optimised use of existing therapies and by developing new cancer drugs.

Summary of current research

The purpose of our research is to better understand the molecular mechanisms of ER action through the use of proteomic, transcriptomic, genomic and epigenomic studies using cell line models of breast cancer and with patient samples. We are extensively using ectopic expression, RNA interference and CRISPR-Cas9 technologies for modelling breast cancer. Our current activities include:

• Define gene regulation by ER in breast cancer cell line models of endocrine therapy responsive and resistance, towards identifying key markers of response and resistance.
• Understanding the role of ER phosphorylation in response and resistance to endocrine therapies (Tamoxifen, Faslodex, Aromatase Inhibitors).
• Identify ER interacting proteins, to understand how different cellular signalling pathways converge on estrogen signalling in breast cancer.
• Determine the importance of DNA damage recognition and repair pathways in regulation of gene expression by ER. In particular, the importance of Base Excision Repair (BER) enzymes uracil DNA glycosylase and thymine DNA glycosylase.
• Importance of enzymes implicated in DNA modification, particularly cytidine deaminases (APOBEC3B) in gene regulation and potential involvement of ER/APOBEC3B interaction in driving cancer mutations
• Develop transcriptional inhibitors, with particular focus on cyclin dependent kinases CDK7 and CDK9, as potential new therapeutic approaches for breast and other cancers.
• Understanding the mechanisms of androgen receptor action in breast and prostate cancer, developed from our work on ER function.

• Breast Cancer Diagnostics Group: The team focusses on the application of circulating cell-free DNA in guiding treatment and in the early detection of recurrence.

Our researchers