The idea
Professor McNeish’s team wanted to develop a new treatment specifically for patients with ovarian clear cell carcinoma (OCCC). To do this, they planned to evaluate the effectiveness of drugs that block IL-6, which could then be used as potential treatments for clear cell ovarian cancer. This would give more understanding of this type of cancer and hopefully pave the way for a clinical trial.
Project background
OCCC is a rare form of ovarian cancer. OCCC can be linked to endometriosis. Chemotherapy doesn’t work as well for OCCC as it does for other forms of ovarian cancer.
Research in the laboratory had shown that a molecule called interleukin-6 (IL-6) may be critical in the development of ovarian clear cell carcinoma. OCCC tumour produced high quantities of IL-6 which encourages tumours to grow and develop their blood supply and makes tumours more resistant to chemotherapy.
Project plan
The research aimed to answer three main questions
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Does blocking IL-6 kill OCCC?
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Is it possible to increase this effect by also interfering with the tumour’s blood supply?
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How and why is IL-6 expressed at very high levels in OCCC? Is there a direct relationship between expression of IL-6 and the two commonest mutations in OCCC?
The team used OCCC cell lines (which are cancer cells that can live in in special conditions in the laboratory) and samples from women with OCCC taking part in a new clinical trial. They used mice to find out whether blocking IL-6 can slow the growth of OCCC.
Research results
Researchers showed that OCCC generates large quantities of IL-6. Unfortunately, blocking IL-6 alone does not have an obvious tumour killing effect. Production of IL-6 appears to explain why women with OCCC are anaemic and have high platelet counts.
Researchers showed that inhibiting IL-6 reduces blood vessels growing into OCCC. Treatment with a combination of IL-6 blockers and VEGF inhibitors reduces the number of blood vessels further and reversed anaemia. However, combining IL-6 blockade with VEGF inhibition did not appear to kill OCCC tumours or stop cells from growing.
Macrophages are white blood cells that normally clear up dead cells in the body. However in cancer sometimes macrophages help cancer cells to grow. Researchers found that blocking IL-6 appeared to stop macrophages from helping the cancer and change their behaviour to inhibit the cancer.
Why is this research important to those affected by ovarian cancer?
This project adds to the overall picture of ovarian clear cell carcinoma. Future work is still needed to determine why OCCC generates such large quantities of IL-6 and to ask whether combining IL-6 inhibitors with other anti-cancer treatments may be helpful in treating this rare form of ovarian cancer.
Fact file
Researcher: Professor Ian McNeish
Institution: University of Glasgow
Project dates: April 2017 to October 2019
Funding awarded: £179,556
Project status: complete
