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Preventing chemotherapy resistance in ovarian cancer

Funded by Wellbeing of Women, Dr Sarah McClelland has been investigating why some of the most common ovarian cancers become resistant to chemotherapy

High-grade serous ovarian cancer is the most common type of ovarian cancer, the deadliest gynaecological cancer in the Western world.

This ovarian cancer is particularly lethal because, even if treatment is successful at first, it often becomes resistant to chemotherapy – making it effectively untreatable.

Supported by Wellbeing of Women, Dr Sarah McClelland, Reader in Cancer Cell Biology at Barts Cancer Institute, Queen Mary University of London, has been investigating why this occurs and if there is a way to slow down or prevent this ‘chemotherapy resistance’ in women with high-grade serous ovarian cancer.

Her team has discovered two previously unknown relationships between specific mechanisms that cancer cells use to ‘reshuffle’ their genetic material and the cancer’s response to chemotherapy drugs.


What is high-grade serous ovarian cancer?

This form of the disease is a sub-type of epithelial ovarian cancer, which develops in the epithelial tissue that lines the ovaries and fallopian tubes. More than 6 in every 10 cases of epithelial ovarian cancer are high-grade serous[LG1]

Chemotherapy is a common treatment for high-grade serous ovarian cancer, but it often returns and becomes resistant to this treatment. This makes it much more challenging to treat. Dr McClelland Wellbeing of Women researcher

High-grade serous ovarian cancer is known to have high rates of chromosomal instability, which is when the chromosomes inside cancer cells change a lot. Researchers believe it is this that may be causing the cells to become resistant to chemotherapy.

Visit our information page to learn more about what is ovarian cancer.

Preventing chemotherapy resistance in ovarian cancer

Dr McClelland and her team studied cell lines derived from tissue samples from women with high-grade serous ovarian cancer. 

They were able to perform the first detailed investigation into the inner genomic workings of these cancer cells and discovered two key mechanisms that contribute to chemotherapy resistance.

  1. The behaviour of microtubules – small, hollow tubes that help control normal cell division and function – becomes chaotic (deregulated).
  2. Elevated levels of stress on the DNA replication process. This replication happens naturally as cells within the body grow and divide, but stress, such as DNA damage, make it difficult for this process to occur and can cause genomic instability. 

Excitingly, researchers also discovered that these mechanisms could indicate whether particular treatments would be effective for different women with high-grade serous ovarian cancer. This knowledge could eventually help support doctors’ prescribing decisions.

Dr McClelland says:

“About 21 women are diagnosed with ovarian cancer every day in the UK and most of them will be told they have high-grade serous cancer.

“Treatment can be gruelling and the chance of this type of cancer returning is high. Imagine being told that your cancer has returned. That’s devastating enough, but what if you were then told that the chemotherapy that destroyed it originally will no longer work? 

“Thanks to Wellbeing of Women funding this important study, our findings should give women hope that they no longer have to hear those words."

Not only have we been able to understand some of the mechanisms responsible for chemotherapy resistance so that we can now begin looking at ways to slow down or prevent this from occurring, but we have also identified how these same mechanisms can predict a woman’s response to certain treatments Dr McClelland

By looking at how cells react to different kinds of stress, like radiation or DNA damage, researchers were able to deduce if a group of drugs called PARP inhibitors will work well or not.

They were also able to assess the effectiveness of a class of chemotherapy drugs called taxanes by examining the extent of deregulation of microtubule dynamics. This could potentially become the first biomarker to predict how well a person might respond to taxane-based treatment.

What’s next?

Further research is required to confirm Dr McClelland’s work and move it from the laboratory into the clinic.

If successful, the biomarkers identified by Dr McClelland and her team could be used in clinical trials to develop new, personalised treatments and inform clinical decision-making.

Wellbeing of Women is funding several research projects to help improve treatment and care for women with gynaecological cancer. Other studies focusing on ovarian cancer include: