Fighting Breast Cancer: Repurposing a Diabetes Drug to Boost Immunotherapy

Breast cancer is the most common cancer in the UK, sadly leading to around 11,500 deaths every year. While many patients are treated successfully, for others the disease will return.

Immunotherapy is a revolutionary treatment that trains the body’s own immune system to find and kill cancer cells. It offers the hope of a long-term solution, can work when other treatments fail, and typically has far fewer harmful side effects than traditional treatments like chemotherapy. By training the immune system, it can also keep cancer away for longer.

However, immunotherapy is currently less effective against breast cancer than it is for other cancers. This is what Associate Professor and Consultant in Medical Oncology Dr. Constantinos Savva and his collaborators aim to change.

Dr. Savva’s initial studies have uncovered a promising link between metabolism and the immune response in breast cancer patients. His research shows that the commonly used anti-diabetic drug, Metformin, can help:

• Boost the immune response within tumours.
• It was found to increase the number of tumour-infiltrating immune cells, especially in patients with a high body mass index (BMI).

This led to the creation of the research project, IMPACT (Targeting Immuno-Metabolic Pathways to overcome obesity-Associated breast Cancer resistance to immunoTherapy). The core idea is that obesity-related changes in the body’s metabolism are making immunotherapy less effective, and this effect can be reversed by using drugs like Metformin.

The IMPACT project will lay the foundation for a five-year clinical trial by:

1. Analysing Patient Data: Correlating the metabolic profiles and body composition of patients with their tumour-specific immune signatures and how well they respond to immunotherapy.
2. Laboratory Studies: Mechanistically determining how a patient’s metabolism (and drugs like Metformin) affect the anti-tumour immune response in pre-clinical models.

Dr. Savva will be based at the Centre for Cancer Immunology in Southampton, the UK’s first centre of its kind. He is collaborating with top institutions to advance this work:

• Francis Crick Institute to enhance the understanding of immune resistance.
• University College London (UCL) and AI colleagues at Southampton to harness advanced imaging, metabolomics, and transcriptomic techniques.

The discoveries made through this research are expected to lead to novel immunological and metabolic “signatures” that can be used to better predict which patients will benefit most from immunotherapy. Crucially, the findings will guide the design of interventional clinical trials targeting patients’ metabolic profiles to improve breast cancer outcomes and give new hope to patients and their families.