TOGETHER, FUNDING RESEARCH that will enable women with gynaecological cancer to live longer, better lives.

Researcher Story

14 April 2021

DR GEORGE AU-YEUNG SHARES WHAT MOTIVATES HIM TO RUN THE IGNITE TRIAL

Women with ovarian cancer are amazingly resilient and cope with a really big roller coaster ride, despite them having pretty dismal outcomes. That’s something that I really admired, so was hoping to try and improve that for them.

IGNITE is designed for a specific subset of patients with ovarian cancer that have high levels of a particular protein called Cyclin E1. We have previously shown that patients with these tumours tend to respond poorly to conventional types of chemotherapies and also do not tend to respond to some of the newer drugs that have been made available. So the trial is about establishing a new type of treatment for these women who typically have few good treatment options left – using a drug called Adavosertib to specifically target these types of cancer.

It works to stop cells from dividing; we know that cancers that have high levels of Cyclin E in the tumour are reliant on this pathway and this drug blocks that pathway, that’s why we think these tumours respond well to it. The unique thing about IGNITE is that we’re selecting patients on the basis of a particular characteristic in the tumour – we think these tumours will respond better to the drug as opposed to an unselected group of patients with ovarian cancer. This is one of the first studies around the world to specifically identify patients with a high level of Cyclin E1 and give them treatment based on that protein. We’re aware of only one other trial around the world that’s doing that.

The plan is to understand why some people’s tumours respond really well and why other people’s tumours don’t tend to respond that well, so that we can then design the next study to help those patients where this drug for example by itself might not work very well. From my personal perspective, I see this study as the first step. We’re still working hard to try & find new treatment options for women with ovarian cancer and I think the IGNITE study is a good example of one that will hopefully prove to be a really good one. We would like to think would become part of routine testing in the future. The importance of this study is that if we show that this drug is effective, then it convinces people that we should be testing for Cyclin E1 routinely.

Historically, ovarian cancer has been treated as one disease with surgery and chemotherapy. Then when it recurs again, the choice of chemotherapy is based largely on people’s side effects of treatment profile and their other health conditions, as opposed to it being a selection of treatment that depends on what their type of cancer is and how likely it is to respond to treatment. Probably over the last 5 years there’s been an increase in understanding of ovarian cancers that are related to the BRCA 1 and 2 gene, or other genes that relate to BRCA 1 and 2 function. Those are the ones that tend to respond best to PARP inhibitors, which have been very much a huge advance in the management of ovarian cancer, and we’re doing testing for those genes routinely now in clinical practice. However, tumours that have high levels of Cyclin E1 do not tend to respond well to PARP inhibitors, which is why trials like IGNITE are so important.

I think particularly when patients come off the back of treatment like chemotherapy that’s been either not very well tolerated or not working very effectively, to then be able to have a treatment that’s also oral makes a big difference. They don’t have to have repeated infusions and injections and come into the hospital every week for treatments, and they can do this in the convenience of their own home. I think that’s been really promising and exciting.

The current trial is for patients whose cancers have recurred and they’ve failed lots of different treatment options. In the future, what we would like is to be able to offer this treatment to women earlier in their disease course, to impact their disease earlier and hopefully prevent their cancer from recurring and coming back and being harder and harder to treat. Ultimately, we’re all hoping that we’re going to be able to cure ovarian cancer. I think that’s what our patients want from us. I don’t know whether that’s achievable or not but I know that we as an ovarian cancer research community are committed to achieving better outcomes for our patients.

This sort of research is really challenging. We’ve been trying to get trials of Cyclin E1 patients open for about 6 years, part of that is related to having the funding to support a study. We recognise that funding for research is becoming harder and harder to seek and to obtain. Having support for IGNITE and the other Cyclin E1 associated studies is really crucial, we wouldn’t be able to push forward without people’s support.

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