Dr Andy Green - The role of ferroptosis in luminal breast cancer
Lay summary
Background: Many women are diagnosed with luminal (ER+) breast cancer, which is the most common kind. Unfortunately, even after treatment, it can come back. Scientists are interested in a new process called ferroptosis, which is a way cells die that involves iron. While they've looked at this in other breast cancers, such as triple negative breast cancer, we need to do more research to see if it plays a role in luminal breast cancer and if we can use it to develop better treatments.
Aims:This pilot project will study specific proteins related to ferroptosis, a type of cell death, in invasive luminal breast cancer. We want to see how these proteins affect patient outcome, impact cancer growth and progression.
Techniques and Methodology: We're going to study a large collection of breast cancer samples – nearly 3,000 – to see how certain proteins related to ferroptosis are present. We'll use a special technique to visualise these proteins in the cancer tissue. Then, we'll see if the amount of these proteins is linked to things like how aggressive the cancer is, how the body's immune system reacts to it, and how well patients do over time. Finally, we'll work with cancer cells in the lab to see how turning off the genes that control ferroptosis affects cancer growth and spread.
Impact on breast cancer research: This research project is exploring a new way to potentially treat a very aggressive type of luminal breast cancer. Our hope is to find a new treatment for patients who often experience their cancer returning or becoming resistant to current drugs, giving them a better chance for the future.
Scientific summary
Background:
Luminal breast cancer, the most common breast cancer, has up to 40% recurrences after therapy. Ferroptosis, an intracellular iron- dependent form of cell death, is an emerging mechanism. Research to date in the role of ferroptosis in breast cancer however has primarily focussed on triple negative breast cancer. We have identified the gene expression of several key ferroptosis markers (Ferritin light chain, Glucose-6-phosphate dehydrogenase, Glutathione peroxidase 4, Malic Enzyme 1, and Nuclear factor erythroid 2-related factor 2, Solute Carrier Family 39 Member 3) with prognostic potential in luminal breast cancer.
Aims: This pilot grant will confirm the protein expression of key ferroptosis markers in invasive luminal breast cancer and their effect on cell growth and progression to understand their role for their future potential of right sizing treatments.
Techniques and Methodology:
The expression of the ferroptosis-related proteins determined will be determined using immunohistochemistry in a large series of highly characterised luminal breast cancers (n=2,965) with long term follow-up. The protein expression of each marker will be related to clinicopathological parameters, biological- and immune- profiles, and patient outcome. We will use luminal breast cancer cells to investigate the effects on cell growth and progression in vitro using knockdown of ferroptosis gene expression.
Impact on breast cancer research: This pilot study will identify and confirm ferroptosis as a potential therapeutic intervention for highly aggressive luminal BC. Ultimately it will offer a potential new therapeutic option for these patients, whom have an uncertain prognosis due to relapse and/or development of resistance to current therapies.