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Understanding treatment resistance in ovarian cancer

Funded by Wellbeing of Women, Professor Gordon Jayson has been investigating why some women don’t respond well to Avastin (bevacizumab).

A Black female researcher is looking into a microscope in a laboratory. Two other researchers can be seen looking on. The body of a third researcher is in the background

Ovarian cancer is the sixth most common cancer in women. About 1 in 50 women in the UK will be affected by the disease during their lifetime.

Treatment for ovarian cancer includes surgery, chemotherapy and radiotherapy. Some targeted treatments are also available. These ‘lock onto’ a weakness in cancer cells to destroy them rather than affect all cells in the body like chemotherapy. These targeted treatments are generally more effective and have fewer side effects.

One such treatment is bevacizumab (Avastin). It works by blocking the blood supply that tumours need to grow and spread. Studies show that bevacizumab can delay the progression of advanced ovarian cancer when taken in combination with platinum-based chemotherapy, giving women more quality time with their families. In some cases, it also improves long term outcomes.

But researchers have found that not all women with ovarian cancer will benefit from taking it.

Two vials of the treatment bevacizumab (also called Avastin)
Bevacizumab (Avastin)

Professor Gordon Jayson, Professor of Medical Oncology at The Christie NHS Foundation Trust and University of Manchester, has identified biomarkers (tumour tests) that could tell doctors if a woman with the most common type of ovarian cancer may not benefit from bevacizumab.

This discovery was made in studies funded by Wellbeing of Women and suggests that an alternative type of drug might be more effective at targeting tumour blood supply.

Predicting the effectiveness of bevacizumab in ovarian cancer

Prof Jayson and his team studied blood and tumour samples from women with epithelial ovarian cancer.

These samples came from participants of a Phase III clinical trial called ICON7, which investigated the effectiveness of bevacizumab alongside and after chemotherapy in women with ovarian cancer, primary peritoneal cancer – which affects the membrane (peritoneum) that lines the abdominal cavity – or fallopian tube cancer.

In total, 178 women from the trial consented to their pre-chemotherapy-treated tumour samples being used for the purpose of this research and 449 agreed to researchers analysing their blood samples.

In an initial study, the research team identified a group of patients who did not seem to benefit from bevacizumab. To investigate this further, they studied the expression of receptors (small proteins that attach to cells and receive signals to change cell behaviour) for two cytokines on the surface of the tumour cells. Cytokines play an important role in regulating and activating cells in the immune system.

Investigators found that when the receptor for Vascular Endothelial Growth factor (VEGF, the target of bevacizumab) was present in the tumour next to another receptor called c-MET, patients did not benefit from bevacizumab.

The team think that in this situation, when bevacizumab blocks the action of VEGF, c-MET is switched on. If confirmed in further laboratory and clinical studies, the research suggests that patients with this pattern of disease, should receive treatments that block both VEGF and c-MET.

Prof Jayson says:

“Ovarian cancer can be a difficult disease to treat because diagnosis typically happens at a late stage. Effective treatments are vital for giving women as much time as possible with their loved ones, so we need to understand how treatments work and for whom they work best.”

These findings need to be confirmed in further laboratory and clinical trials. If these further studies confirm the findings, patients with this molecular pattern of ovarian cancer should be treated with drugs that block both VEGF and c-MET. Prof Gordon Jayson

What is epithelial ovarian cancer?

Epithelial ovarian cancer is the most common form of the disease, accounting for around 9 in 10 cases. This type of cancer grows in the epithelial tissue that lines the ovaries and fallopian tubes

There are several different sub-types of epithelial ovarian cancer with their own characteristics and treatment challenges. However, drugs such as platinum-based chemotherapy, Bevacizumab and a new group of treatments called PARP inhibitors, should all generally be available as treatment options.

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

Next steps

Prof Jayson and his team plan to design and run a clinical trial investigating potential treatments to reduce levels of c-MET and VEGFR-2 in the body.

Treatments like this will be especially useful for women with high levels of these proteins in whom we now know bevacizumab is not effective.

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: