Breast cancers that develop resistance to anti-hormone therapies, such as tamoxifen, can spread throughout the body, which means they can’t be cured. Mutations in the oestrogen receptor (ER) gene are present in 25% of breast cancers that have spread. We need to understand how ER gene mutations cause resistance to anti-hormone therapies.
Professor Ali believes that mutations in the gene that contains the instructions to make the oestrogen receptor (ER) can cause resistance to anti-hormone treatments in secondary breast cancer. To investigate this, he will create breast cancer cells in the lab with mutations in their ER genes. These cells will then be tested in the lab for their response to oestrogen and anti-hormone drugs. Professor Ali will also study these cells when implanted in mice, to understand how quickly they grow and spread throughout the body.
When oestrogen binds to the ER it makes it possible for a protein called CDK7 to also attach to the ER, which drives cancer growth. Mutated ER proteins have a modified shape that allows CDK7 to bind to ER even when oestrogen isn’t present, so making the tumour resistant to anti-hormone treatments. Professor Ali will use the breast cancer cells he’s created to test new drugs he has developed which block the activity of CDK7, which he hopes will identify CDK7 as a new drug target for treating breast cancers that are resistant to anti-hormone drugs.
What difference will this project make?
Professor Ali’s research will help us uncover the role of oestrogen receptor mutations in anti-hormone drug resistance, which could lead to new treatments that improve the chances of survival for thousands of people.
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