The Effect of Metformin on Breast Cancer Metabolism

Researcher: Dr Simon Lord

Location: University of Oxford

Dates:  Sept 2018 – Sept 2022*     Status: In Progress

Funding: £75,000

Research Theme: Therapies

*1 year extension due to COVID

Aims

As part of ABC’s Junior Research Fellowship programme launched in 2018, Dr Simon Lord is the second recipient of the funding. He aims to further understand the role of mitochondria in breast cancer cell growth and metabolism, and how the drug metformin might prevent tumour growth.

Background

Cancer cells need nutrients such as sugars, proteins and fats, in order to grow and make new cancer cells. Cell growth requires energy and mitochondria are like the batteries of the cell, producing the energy that cells need. Mitochondria work by breaking down nutrients to make new building blocks for cell growth. Cancer cells often permanently switch on active mitochondria to grow faster.

Dr Lord and colleagues at the University of Oxford have shown that metformin, a drug commonly used to treat type 2 diabetes, can target mitochondria in breast cancer cells. It seems that metformin makes some breast cancers take up more sugars but has no effect at all on other breast cancers.

Taking up more sugar suggests that metformin changes the metabolism of the cancer cells and it seems that metformin might stop the growth of only those breast cancers that take up more sugar. Dr Lord hopes to determine if mutations in mitochondrial genes can predict if a breast cancer will respond to metformin and take up more sugars.

In addition, it is known that breast cancer is more common in obese than non-obese women, so another aim of this research is to understand how mitochondria in cancer cells might work differently in breast cancers arising in obese women.

To answer this question, breast cancer cells taken from obese and non-obese women are being studied in the laboratory to understand how these cells may use nutrients differently. Genetic techniques are being used to find any differences in genes that control how sugars, fats and amino acids are used in cancer cell metabolism in these two groups of women.

Ultimately, the researchers are keen to understand how different drugs might be used to treat breast cancers that arise in these different groups of women.

Potential benefit for patients

This research may help to identify whether metformin could be used as a new cancer treatment and which patient groups would benefit the most.

Q&A, discussing therapies and the possible effect obesity plays in resisting current treatments

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

Publications

Window of opportunity clinical trial designs to study cancer metabolism. F Aroldi and SR. Lord. Br J Cancer. 2020 Jan 7; 122(1): 45–51. 

Transcriptomic analysis of human primary breast cancer identifies fatty acid oxidation as a target for metformin. SR Lord et al Br J Cancer. 2020 Jan 21; 122(2): 258–265.