Oriel College situated within the University of Oxford provides the base for the Against Breast Cancer Research Fellowships. Created in 2018 to provide research support for some of the country’s leading scientists and clinicians, this 9-year long commitment provides funding for two positions, each for a three year period. Dr Andrew Blackford and Dr Simon Lord are the first recipients of the funding, with proposals aiming to keep us at the forefront of medical research.
Increasing our knowledge of DNA repair mechanisms
We know that cancer is mainly a genetic disease caused by changes – also called mutations – that build up over time in our cells’ DNA. Damage to our DNA happens all the time, but our cells have repair mechanisms to fix this.
One repair mechanism is called ‘DNA double-stranded break repair’. There are two proteins, BRCA1 and BRCA2, that play a critical role in this process however, scientists do not understand exactly how BRCA1 and BRCA2 proteins repair DNA at the molecular level.
Certain regions in the BRCA1 and BRCA2 proteins are thought to be important for stopping tumours forming. It is to better understand the function of these ‘short, linear peptide motifs’ that is the key focus of the research being carried out by Dr Andrew Blackford, one of the Against Breast Cancer Junior Research Fellows at the University of Oxford.
Some of the most effective cancer treatments work by causing DNA damage; therefore, this research aims to increase our understanding of the DNA damage repair at the molecular level. This in turn may help to improve existing treatments as well as develop new ones for breast cancer.
Increasing our knowledge of the role of mitochondria in breast cancer
Cancer cells need nutrients including sugars, proteins and fats to grow and make new cancer cells. Mitochondria are like the batteries of the cell, producing the energy cells need to grow. They 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 Simon Lord and colleagues at the University of Oxford have shown that metformin, a drug commonly used to treat 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. From what we already know, it seems that metformin might stop the growth only of those breast cancers that take up more sugar.
Dr Lord, the second of our Junior Research Fellows at the University of Oxford wishes to determine if mutations in mitochondrial genes can predict if a breast cancer will respond to metformin and take up more sugars. This research may help to find which patients could benefit from metformin.
In addition, it is known that breast cancer is more common in obese than non-obese women; therefore, 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, they are growing breast cancer cells taken from obese and non-obese women 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 cells 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.