3 years ago
1 February, 2021
I studied Biotechnology with Enterprise at the University of Leeds for my undergraduate and Masters degrees. This was a broad subject, but I was particularly interested in understanding how diseases work on a molecular level and how drugs specifically target disease mechanisms.
Cancer is not one disease; many different types occur and behave differently. Even breast cancer has several subtypes that can be classified differently by considering their characteristics and genetic profiles.
The more we understand how these subtypes behave, the better we can identify the most successful therapy for a given person. I find this exciting, and when I saw my PhD project advertised, I knew it was something I wanted to be involved in!
Nuclear receptors are particular proteins found in cells that respond to hormones. They tell the cells what to do by activating DNA to switch genes on or off. This regulates the growth, activity, and death of cells.
A nuclear receptor lots of people have heard of is the estrogen receptor. The estrogen hormone is essential for the normal growth and function of cells in the breast. However, disturbed regulation of oestrogen signalling can lead to cells growing uncontrolled, resulting in cancer. Drugs are available that can stop estrogen binding to its receptor, which stops the growth signals to prevent cancer progression.
I work on triple-negative breast cancer (TNBC), a rare but often aggressive type. It does not have receptors for estrogen, progesterone or HER2. These receptors are the primary targets for breast cancer therapy, so people with TNBC are left with limited treatment options.
My project investigates the glucocorticoid receptor (related to the estrogen receptor) to see how it behaves in TNBC and whether it could be a target for therapy. As part of this, I have been working to create breast cancer spheroids or ‘mini tumours’ that we can use to test treatments on.
Nuclear receptors are interesting as they are important in determining which genes are activated in a cell and how it behaves. If we can understand how this works, we can identify ways to target these mechanisms to prevent disease.
As well as this, currently, around 13% of FDA-approved drugs target nuclear receptors. Suppose we can determine what a particular nuclear receptor does in a specific disease. In that case, we could repurpose some of these already available drugs that have been through safety testing. This is much quicker and cheaper than developing new drugs entirely from scratch!
Many researchers publish the data from their lab work online for anyone to use. We have looked at data from experiments using breast cancer cells treated with different things to see how gene expression changes. This allows us to predict how we think cancer cells behave, identify possible targets for therapy, and predict chemicals that might alter how cells behave. We will then investigate these predictions in the lab to see if they are true.
We have found that the glucocorticoid receptor can promote growth in TNBC. I have been working a lot on creating the spheroid (‘mini tumour’) model. This model is ready to go so we can start testing how different treatments affect tumour growth. Our computer work has also identified several things we think are essential for growth in TNBC. Now we are back in the lab. We can start investigating these!
The glucocorticoid receptor is an essential regulator of inflammation and immunity, and glucocorticoids (the molecules that bind to the receptor) are used to treat chronic inflammatory disorders and some types of cancer. A glucocorticoid receptor is required in normal breast cells to correct cell growth timing during breast development. The glucocorticoid receptor has also been observed in breast cancers, particularly more aggressive and invasive cancers. In TNBC, high levels of the glucocorticoid receptor have been associated with worse survival, and this is what led us to investigate how it could be targeted for therapy.
We hope that a better understanding of the molecular mechanisms of breast cancer will identify new drug targets for people with TNBC. This is important as TNBC is often aggressive, and treatments are more limited for this subtype. Also, if we can identify chemicals that alter the way cells behave, resulting in cancer, this can be used to prevent cancer cases in the future.
I’ve just started the third year of my PhD. Having missed six months of lab time due to COVID disruptions, it will be hectic in the lab! Then it’s on to writing up my results…
Honestly – I’m not sure yet!
I love travelling and exploring new places. During lockdown, I used some of my time to practice my Spanish. So I’d love to revisit South America once it’s safe! Also, I enjoy keeping fit and doing lots of yoga and running. I should have been doing the Leeds half marathon and Tough Mudder this summer (fingers crossed for 2021. But I did manage to do a very rainy Yorkshire Three Peaks!
We’re thankful to Freya Leif for taking the time to talk to us and Dr Laura Matthews for their work to help prevent breast cancer.
This project and the other research projects we are funding are made possible by your generous donations.
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