Therapeutic Targeting of Dormant Breast Cancer Cells

Researcher: Prof Ingunn Holen

Location: University of Sheffield

Dates: Sept 2018 – Mar 2020     Status: Complete

Funding: £19,602

Research Theme: Therapies, Prevention

Aims

Do dormant breast cancer cells that survive chemotherapy become secondary tumours? If so, what are the vital steps in this process?

Professor Ingunn Holen, based at the University of Sheffield, is aiming to improve our understanding of the processes that are required for dormant breast cancer cells to survive chemotherapy and allowing them to regrow into secondary (metastatic) tumours. This will help develop anti-dormancy therapies that could prevent breast cancer recurrence and spread, thereby improving the outcomes for patients.

Background

One characteristic of cancer cells is their uncontrolled rate of cell growth and division. Current chemotherapy treatment works by killing these actively growing cells. However, some breast cancer cells can enter a dormant state, meaning that they are no longer sensitive to the chemotherapy that is designed to eliminate cancer cells that grow and divide. The dormant cancer cells remain in the body after treatment, mainly in the bone marrow, where they are hiding in plain sight. Some of these dormant cancer cells may one day be triggered to start to grow and form new tumours, as well as spread to other parts of the body.

We don’t yet understand the mechanisms that cancer cells rely on to survive in this dormant state, or what triggers them to start growing again. Prof Holen aims to understand this in more detail by investigating the differences between chemotherapy-treated and untreated cells, to identify markers that drive dormancy and resistance to therapy. She will also investigate whether dormant cells have a greater potential to cause tumour growth compared to rapidly growing cancer cells.

Potential benefit for patients

There are currently no specific treatments that can prevent breast cancer spread. Understanding why and how cancer cells become dormant may identify targets that can be used to develop novel therapies that will either eliminate dormant cancer cells, or ensure they remain dormant indefinitely, in order to prevent regrowth of secondary tumours.

Project Results and Impact

Project results have included: 

• Dormant cells are capable of forming new tumours after chemotherapy treatment.

• The removal of dormant cells reduces the ability of cancer cells to form new tumours. Both of these findings support Prof Holen’s hypothesis that dormant cells survive chemotherapy, retain their ability to regrow and play a major role in secondary tumour recurrence.

• Identification of 15 genes that may help dormant cells to survive chemotherapy. These genes may be potential candidates for new therapeutics. Further investigation will be needed to see how altering these genes might affect dormant cancer cells.

“The seed funding has allowed us to carry out important studies of how breast cancer cells survive chemotherapy by entering a state of dormancy.”

Professor Ingunn Holen

ABC has continued our support of Prof Holen’s exciting research into dormant breast cancer cells and are supporting a follow-on project. You can find out more about the vital research being undertaken by Professor Holen and her team at the University of Sheffield’s Department of Oncology & Metabolism here.

Q&A, discussing detection and dormant breast cancer cells

As part of our regular Research Q&A series, Professor Holen took the time to answer questions about her research which were posed by supporters of Against Breast Cancer;