4 years ago
15 December, 2019
Part of this programme supports emerging scientists in breast cancer research. With your support, we have been able to fund a number of PhD students. We met up with one of our current PhD students, Alex Websdale from Leeds University, to learn more about his research project and what he hopes we will learn.
I want to understand how we can prevent the recurrence of breast cancer called “triple negative” breast cancer. This cancer has a worse prognosis than other types of breast cancer. It cannot be treated with common hormonal therapies. Patients with “triple negative” breast cancer must undergo non-hormone targeting chemotherapy, which may have worse side effects.
A previous study has shown that certain products of cholesterol breakdown in our body, called oxysterols, can increase the production of chemotherapy drug export pumps in the brain. Production of these pumps in cancer cells makes them “chemotherapy resistant” and no longer respond to chemotherapy, making recurrence more likely. I want to explore if patients could benefit from a reduction in cholesterol when they are undergoing chemotherapy.
Ultimately, with my investigations, I want to have an impact on identifying how these cancer cells can be targeted with therapy. Preventing secondary breast cancer and increasing survival rates.
Oxysterols are by-products of cholesterol breakdown. Cholesterol is a fat-like substance made by the body and found in some foods. It is essential for good health and is found in every cell in your body. However, having a high level of cholesterol in your blood can harm your health. The difference between oxysterols and cholesterol is the addition of oxygen and hydrogen to the molecule.
Tumour cells respond to high internal levels of oxysterols by producing pumps in their cell walls to push oxysterols out again. However, these pumps also remove helpful substances, such as chemotherapy agents, which can lead to chemotherapy resistance in cancer cells. Oxysterols are also associated with the promotion of secondary tumour growths called metastases.
It was only recently that oxysterols have been linked to cancer, and there’s a lot still to investigate. Also, as oxysterols are a product of cholesterol breakdown, this may suggest a link between high-cholesterol diets and worse breast cancer outcomes.
A study from our lab has shown that triple-negative breast cancers are more responsive to oxysterol signalling than some other breast cancer types. If oxysterols act through similar methods on breast cancer cells as cells in the brain, this could suggest that triple-negative breast cancers are more likely to become chemotherapy-resistant through oxysterols than other types of breast cancer.
Cancer research has always been a field that has interested me, though I didn’t have much experience with it during my undergraduate degree. When looking for PhDs this was a great opportunity to work in the field of cancer with an interesting concept behind it.
Hopefully, it could improve treatment for non-hormone-responsive cancers. And help reduce the chance of breast cancer recurrence following initial diagnosis.
Thanks to Alex for sharing this background in his research project. To find out more about our current and past research projects, see our research.
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