27 July, 2022

The first of two BCUK’s co-funded PhD studentships, awarded to Alex Websdale, has recently come to an end. Alex’s project was co-funded by the University of Leeds and supervised by Dr James Thorne – who was awarded a BCUK grant to investigate the role of oxysterols in breast cancer.

We are very excited to hear how his project went, what he found out and what he wants to do now that he has submitted his doctoral thesis and been awarded a PhD.

Let’s talk about the BCUK-funded research project you recently completed; what was this looking at?

My primary goal was to investigate the mechanisms through which cholesterol can cause resistance to chemotherapy in triple-negative breast cancers. Ineffective chemotherapy increases the likelihood that the treatment will not kill all remaining cancer cells, which can increase the chance of cancer recurrence. By identifying a mechanism that causes chemotherapy resistance, methods could be designed to overcome resistance.

What were your most important findings?

I found that products of cholesterol metabolism, called oxysterols, activate a cellular pathway in triple-negative breast cancers linked to how chemotherapy drugs are processed. Levels of the oxysterols in patient’s tumour samples predicted whether the patient was going to relapse or not.

I also looked into where the oxysterols were being made and found that a type of support cells in the tumour, known as fibroblasts, produce oxysterols at quite a high level and that these cells merely being close to a cancer cell can actually activate the chemotherapy processing pathway in the cancer cells. We suspect the presence of these fibroblast support cells may allow the tumour to resist the chemotherapy drugs.

How will your research be used, and what difference will your findings make?

My research needs to be built on by others before it can be translated into clinical. We now have a possible mechanism to explore that could explain why the link between cholesterol and cancer has been so contentious over recent years. Perhaps some cancers in some individuals may respond to anti-cholesterol interventions. My research will be used to explore which patients may benefit. Further research is definitely needed in this field before any changes to patient care can be considered.

Were there hurdles you had to overcome? Did the pandemic affect your research?

The first lockdown was a big challenge to overcome as I couldn’t conduct any lab-based research. Instead, I changed my focus to meta-analyses, which group and summarise previously published data to see if there is a consistent trend across similar experiments performed by different lab groups. Re-entry to labs presented a different challenge due to the limitations on capacity, which slowed down my speed of data generation.

What has Breast Cancer UK’s support meant for your research?

Breast Cancer UK has been fantastic for my research and it wouldn’t be possible without them. They were very considerate of the troubles the pandemic caused and were all too happy to offer me an extension to my project so I could complete my lab work. If not for this extension, data that is currently being prepared for publication would not have been generated.

What are your plans now?

I’m currently working in the tumour profiling department for a company that develops anti-cancer immunotherapy products.

What inspired you to become a scientist?

I’ve always wanted to help improve patient outcomes and this career allows me to work towards that every day.

Read his last interview

As desperate as we are to understand the causes of breast cancer, we firmly believe that this can be done without harm to animals. Please make a donation of your choice today to help our scientists undertake world-class research. Thank you.

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